Targeting Immune Checkpoints: Basic Signaling Pathways and Clinical Translation in Cancer Therapeutics

Abstract

Immune checkpoints, the key gatekeepers of immune homeostasis, have become the central targets of modern cancer immunotherapy. These regulatory pathways, composed of co-suppressive and co-stimulatory molecules, enable the immune system to distinguish between self and non-self while preventing excessive tissue damage. However, tumor cells strategically block these protective mechanisms through aberrant expression of checkpoint ligands, creating an immunosuppressive microenvironment that promotes tumor immune evasion and metastatic progression. Yet, immune checkpoint therapy is not universally applied due to its specific mechanisms. This review systematically describes the immune checkpoints that function on various types of immune cells, as well as their molecular structure and functional diversity, and elucidates their role in achieving tumor immune escape. We analyze the clinical translation of immune checkpoint inhibitors (ICIs) and their combination therapies. In addition, we combine preclinical findings with clinical trial data to provide a comprehensive framework for understanding the mechanisms of action and clinical applications of immune checkpoints, as well as to present the challenges in terms of immune-related adverse events of ICIs. This review provides a valuable perspective for developing next-generation immunotherapies and optimizing personalized treatment strategies.

Keywords

immune checkpoint / immune escape / immunotherapy / monoclonal antibody

References

[1] X. Zhou, X. Liu, and L. Huang, “Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention,” Advanced Functional Materials 31, no. 5 (2021): 2006220.

[2] K. Esfahani, L. Roudaia, N. Buhlaiga, S. V. Del Rincon, N. Papneja, and W. H. Miller , “A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future,” supplement, Current Oncology 27, no. S2 (2020): 87-97.

[3] D. N. Khalil, E. L. Smith, R. J. Brentjens, and J. D. Wolchok, “The Future of Cancer Treatment: Immunomodulation, CARs and Combination Immunotherapy,” Nature Reviews Clinical Oncology 13, no. 5 (2016): 273-290.

[4] T. Fan, M. Zhang, J. Yang, Z. Zhu, W. Cao, and C. Dong, “Therapeutic Cancer Vaccines: Advancements, Challenges, and Prospects,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 450.

[5] L. H. Butterfield and Y. G. Najjar, “Immunotherapy Combination Approaches: Mechanisms, Biomarkers and Clinical Observations,” Nature Reviews Immunology 24, no. 6 (2024): 399-416.

[6] L. Zhang, Z. Wang, K. Liu, et al., “Targets of Tumor Microenvironment for Potential Drug Development,” MedComm - Oncology 3, no. 1 (2024): e68.

[7] A. Kalbasi and A. Ribas, “Tumour-Intrinsic Resistance to Immune Checkpoint Blockade,” Nature Reviews Immunology 20, no. 1 (2020): 25-39.

[8] X. He and C. Xu, “Immune Checkpoint Signaling and Cancer Immunotherapy,” Cell Research 30, no. 8 (2020): 660-669.

[9] R. A. Lin, J. K. Lin, and S. Y. Lin, “Mechanisms of Immunogenic Cell Death and Immune Checkpoint Blockade Therapy,” Kaohsiung Journal of Medical Sciences 37, no. 6 (2021): 448-458.

[10] J. H. Esensten, Y. A. Helou, G. Chopra, A. Weiss, and J. A. Bluestone, “CD28 Costimulation: From Mechanism to Therapy,” Immunity 44, no. 5 (2016): 973-988.

[11] M. C. Pulanco, A. T. Madsen, A. Tanwar, D. T. Corrigan, and X. Zang, “Recent Advancements in the B7/CD28 Immune Checkpoint Families: New Biology and Clinical Therapeutic Strategies,” Cellular & Molecular Immunology 20, no. 7 (2023): 694-713.

[12] N. Curdy, O. Lanvin, C. Laurent, J. J. Fournié, and D. M. Franchini, “Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression,” Trends in Cell Biology 29, no. 10 (2019): 777-790.

[13] K. M. Heinhuis, W. Ros, M. Kok, N. Steeghs, J. H. Beijnen, and J. H. M. Schellens, “Enhancing Antitumor Response by Combining Immune Checkpoint Inhibitors With Chemotherapy in Solid Tumors,” Annals of Oncology 30, no. 2 (2019): 219-235.

[14] T. Tang, X. Huang, G. Zhang, Z. Hong, X. Bai, and T. Liang, “Advantages of Targeting the Tumor Immune Microenvironment Over Blocking Immune Checkpoint in Cancer Immunotherapy,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 72.

[15] T. Shekarian, S. Valsesia-Wittmann, J. Brody, et al., “Pattern Recognition Receptors: Immune Targets to Enhance Cancer Immunotherapy,” Annals of Oncology 28, no. 8 (2017): 1756-1766.

[16] S. L. Topalian, J. M. Taube, R. A. Anders, and D. M. Pardoll, “Mechanism-Driven Biomarkers to Guide Immune Checkpoint Blockade in Cancer Therapy,” Nature Reviews Cancer 16, no. 5 (2016): 275-287.

[17] W. Li, F. Wang, R. Guo, Z. Bian, and Y. Song, “Targeting Macrophages in Hematological Malignancies: Recent Advances and Future Directions,” Journal of Hematology & Oncology 15, no. 1 (2022): 110.

[18] K. Huntoon, W. Jiang, and B. Y. S. Kim, “Waking Immune-Resistant Tumors With Neddylation,” Journal of Clinical Investigation 133, no. 4 (2023): e167894.

[19] J. S. O'Donnell, M. W. L. Teng, and M. J. Smyth, “Cancer Immunoediting and Resistance to T Cell-Based Immunotherapy,” Nature Reviews Clinical Oncology 16, no. 3 (2019): 151-167.

[20] R. Bouwstra, T. van Meerten, and E. Bremer, “CD47-SIRPα Blocking-Based Immunotherapy: Current and Prospective Therapeutic Strategies,” Clinical and Translational Medicine 12, no. 8 (2022): e943.

[21] B. Ruffell and L. M. Coussens, “Macrophages and Therapeutic Resistance in Cancer,” Cancer Cell 27, no. 4 (2015): 462-472.

[22] M. Feng, W. Jiang, B. Y. S. Kim, C. C. Zhang, Y. X. Fu, and I. L. Weissman, “Phagocytosis Checkpoints as New Targets for Cancer Immunotherapy,” Nature Reviews Cancer 19, no. 10 (2019): 568-586.

[23] N. Lin, Y. Song, and J. Zhu, “Immune Checkpoint Inhibitors in Malignant Lymphoma: Advances and Perspectives,” Chinese Journal of Cancer Research 32, no. 3 (2020): 303-318.

[24] Y. Hu, Q. Hu, Y. Li, et al., “γδ T Cells: Origin and Fate, Subsets, Diseases and Immunotherapy,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 434.

[25] S. Cormican and M. D. Griffin, “Human Monocyte Subset Distinctions and Function: Insights From Gene Expression Analysis,” Frontiers in Immunology 11 (2020): 1070.

[26] M. Guilliams and F. R. Svedberg, “Does Tissue Imprinting Restrict Macrophage Plasticity?,” Nature Immunology 22, no. 2 (2021): 118-127.

[27] X. Wu, Z. Wang, J. Shi, et al., “Macrophage Polarization Toward M1 Phenotype Through NF-κB Signaling in Patients With Behçet's Disease,” Arthritis Research & Therapy 24, no. 1 (2022): 249.

[28] M. Ö. Celik, D. Labuz, J. Keye, R. Glauben, and H. Machelska, “IL-4 Induces M2 Macrophages to Produce Sustained Analgesia via Opioids,” JCI Insight 5, no. 4 (2020): e133093.

[29] M. Akhtari, S. J. Zargar, M. Vojdanian, A. Jamshidi, and M. Mahmoudi, “Monocyte-Derived and M1 Macrophages From Ankylosing Spondylitis Patients Released Higher TNF-α and Expressed More IL1B in Response to BzATP Than Macrophages From Healthy Subjects,” Scientific Reports 11, no. 1 (2021): 17842.

[30] G. R. Gunassekaran, S. M. Poongkavithai Vadevoo, M. C. Baek, and B. Lee, “M1 Macrophage Exosomes Engineered to Foster M1 Polarization and Target the IL-4 Receptor Inhibit Tumor Growth by Reprogramming Tumor-Associated Macrophages Into M1-Like Macrophages,” Biomaterials 278 (2021): 121137.

[31] E. Nagata, H. Masuda, T. Nakayama, et al., “Insufficient Production of IL-10 From M2 Macrophages Impairs In Vitro Endothelial Progenitor Cell Differentiation in Patients With Moyamoya Disease,” Scientific Reports 9, no. 1 (2019): 16752.

[32] K. Yang, Y. Xie, L. Xue, et al., “M2 Tumor-Associated Macrophage Mediates the Maintenance of Stemness to Promote Cisplatin Resistance by Secreting TGF-β1 in Esophageal Squamous Cell Carcinoma,” Journal of Translational Medicine 21, no. 1 (2023): 26.

[33] D. Tu, J. Dou, M. Wang, H. Zhuang, and X. Zhang, “M2 Macrophages Contribute to Cell Proliferation and Migration of Breast Cancer,” Cell Biology International 45, no. 4 (2021): 831-838.

[34] Z. Hu, W. Li, S. Chen, et al., “Design of a Novel Chimeric Peptide via Dual Blockade of CD47/SIRPα and PD-1/PD-L1 for Cancer Immunotherapy,” Science China Life Sciences 66, no. 10 (2023): 2310-2328.

[35] M. Yazdani, Z. Gholizadeh, A. R. Nikpoor, N. Mohamadian Roshan, M. R. Jaafari, and A. Badiee, “Ex Vivo Dendritic Cell-Based (DC) Vaccine Pulsed With a Low Dose of Liposomal Antigen and CpG-ODN Improved PD-1 Blockade Immunotherapy,” Scientific Reports 11, no. 1 (2021): 14661.

[36] I. Terrén, A. Orrantia, J. Vitallé, O. Zenarruzabeitia, and F. Borrego, “NK Cell Metabolism and Tumor Microenvironment,” Frontiers in Immunology 10 (2019): 2278.

[37] Z. Lin, A. A. Bashirova, M. Viard, et al., “HLA Class I Signal Peptide Polymorphism Determines the Level of CD94/NKG2-HLA-E-Mediated Regulation of Effector Cell Responses,” Nature Immunology 24, no. 7 (2023): 1087-1097.

[38] E. Vivier, D. Artis, M. Colonna, et al., “Innate Lymphoid Cells: 10 Years on,” Cell 174, no. 5 (2018): 1054-1066.

[39] X. Shi, X. Cheng, A. Jiang, et al., “Immune Checkpoints in B Cells: Unlocking New Potentials in Cancer Treatment,” Advanced Science 11, no. 47 (2024): e2403423.

[40] L. Bod, Y. C. Kye, J. Shi, et al., “B-Cell-Specific Checkpoint Molecules That Regulate Anti-Tumour Immunity,” Nature 619, no. 7969 (2023): 348-356.

[41] M. Wu, Q. Huang, Y. Xie, et al., “Improvement of the Anticancer Efficacy of PD-1/PD-L1 Blockade via Combination Therapy and PD-L1 Regulation,” Journal of Hematology & Oncology 15, no. 1 (2022): 24.

[42] A. Salmaninejad, S. F. Valilou, A. G. Shabgah, et al., “PD-1/PD-L1 Pathway: Basic Biology and Role in Cancer Immunotherapy,” Journal of Cellular Physiology 234, no. 10 (2019): 16824-16837.

[43] K. M. Viramontes, E. N. Neubert, J. M. DeRogatis, and R. Tinoco, “PD-1 Immune Checkpoint Blockade and PSGL-1 Inhibition Synergize to Reinvigorate Exhausted T Cells,” Frontiers in Immunology 13 (2022): 869768.

[44] A. Cercek, M. Lumish, J. Sinopoli, et al., “PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer,” New England Journal of Medicine 386, no. 25 (2022): 2363-2376.

[45] M. de Miguel and E. Calvo, “Clinical Challenges of Immune Checkpoint Inhibitors,” Cancer Cell 38, no. 3 (2020): 326-333.

[46] M. Ahmadzadeh, L. A. Johnson, B. Heemskerk, et al., “Tumor Antigen-Specific CD8 T Cells Infiltrating the Tumor Express High Levels of PD-1 and Are Functionally Impaired,” Blood 114, no. 8 (2009): 1537-1544.

[47] M. Borgeaud, J. Sandoval, M. Obeid, et al., “Novel Targets for Immune-Checkpoint Inhibition in Cancer,” Cancer Treatment Reviews 120 (2023): 102614.

[48] H. Dong, S. E. Strome, D. R. Salomao, et al., “Tumor-Associated B7-H1 Promotes T-Cell Apoptosis: A Potential Mechanism of Immune Evasion,” Nature Medicine 8, no. 8 (2002): 793-800.

[49] M. E. Keir, M. J. Butte, G. J. Freeman, and A. H. Sharpe, “PD-1 and Its Ligands in Tolerance and Immunity,” Annual Review of Immunology 26 (2008): 677-704.

[50] A. H. Sharpe, E. J. Wherry, R. Ahmed, and G. J. Freeman, “The Function of Programmed Cell Death 1 and Its Ligands in Regulating Autoimmunity and Infection,” Nature Immunology 8, no. 3 (2007): 239-245.

[51] Y. Liang, L. Li, Y. Chen, J. Xiao, and D. Wei, “PD-1/PD-L1 Immune Checkpoints: Tumor vs Atherosclerotic Progression,” Clinica Chimica Acta 519 (2021): 70-75.

[52] L. M. Francisco, P. T. Sage, and A. H. Sharpe, “The PD-1 Pathway in Tolerance and Autoimmunity,” Immunological Reviews 236 (2010): 219-242.

[53] V. A. Boussiotis, “Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway,” New England Journal of Medicine 375, no. 18 (2016): 1767-1778.

[54] J. Tan, Q. Xue, X. Hu, and J. Yang, “Inhibitor of PD-1/PD-L1: A New Approach May Be Beneficial for the Treatment of Idiopathic Pulmonary Fibrosis,” Journal of Translational Medicine 22, no. 1 (2024): 95.

[55] S. Liu, H. Wang, X. Shao, et al., “Advances in PD-1 Signaling Inhibition-Based Nano-Delivery Systems for Tumor Therapy,” Journal of Nanobiotechnology 21, no. 1 (2023): 207.

[56] H. Yamaguchi, J. M. Hsu, W. H. Yang, and M. C. Hung, “Mechanisms Regulating PD-L1 Expression in Cancers and Associated Opportunities for Novel Small-Molecule Therapeutics,” Nature Reviews Clinical Oncology 19, no. 5 (2022): 287-305.

[57] X. Wang, L. Yang, F. Huang, et al., “Inflammatory Cytokines IL-17 and TNF-α Up-Regulate PD-L1 Expression in Human Prostate and Colon Cancer Cells,” Immunology Letters 184 (2017): 7-14.

[58] J. H. Cha, L. C. Chan, C. W. Li, J. L. Hsu, and M. C. Hung, “Mechanisms Controlling PD-L1 Expression in Cancer,” Molecular Cell 76, no. 3 (2019): 359-370.

[59] F. Krutzek, K. Kopka, and S. Stadlbauer, “Development of Radiotracers for Imaging of the PD-1/PD-L1 Axis,” Pharmaceuticals 15, no. 6 (2022): 747.

[60] M. Barsch, H. Salié, A. E. Schlaak, et al., “T-Cell Exhaustion and Residency Dynamics Inform Clinical Outcomes in Hepatocellular Carcinoma,” Journal of Hepatology 77, no. 2 (2022): 397-409.

[61] L. Wang, Z. Yang, F. Guo, et al., “Research Progress of Biomarkers in the Prediction of Anti-PD-1/PD-L1 Immunotherapeutic Efficiency in Lung Cancer,” Frontiers in Immunology 14 (2023): 1227797.

[62] E. Khatoon, D. Parama, A. Kumar, et al., “Targeting PD-1/PD-L1 Axis as New Horizon for Ovarian Cancer Therapy,” Life Sciences 306 (2022): 120827.

[63] C. D. Nishimura, M. C. Pulanco, W. Cui, L. Lu, and X. Zang, “PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies,” Trends in Molecular Medicine 27, no. 3 (2021): 207-219.

[64] J. Zhang, Y. Yan, J. Li, R. Adhikari, and L. Fu, “PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake,” Frontiers in Pharmacology 11 (2020): 722.

[65] M. Yi, X. Zheng, M. Niu, S. Zhu, H. Ge, and K. Wu, “Combination Strategies With PD-1/PD-L1 Blockade: Current Advances and Future Directions,” Molecular Cancer 21, no. 1 (2022): 28.

[66] M. Yi, M. Niu, L. Xu, S. Luo, and K. Wu, “Regulation of PD-L1 Expression in the Tumor Microenvironment,” Journal of Hematology & Oncology 14, no. 1 (2021): 10.

[67] M. Jalili-Nik, A. Soltani, B. Mashkani, H. Rafatpanah, and S. I. Hashemy, “PD-1 and PD-L1 Inhibitors Foster the Progression of Adult T-Cell Leukemia/Lymphoma,” International Immunopharmacology 98 (2021): 107870.

[68] Y. Han, D. Liu, and L. Li, “PD-1/PD-L1 Pathway: Current Researches in Cancer,” American Journal of Cancer Research 10, no. 3 (2020): 727-742.

[69] Y. Liu, Y. Wang, Y. Yang, et al., “Emerging Phagocytosis Checkpoints in Cancer Immunotherapy,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 104.

[70] J. Hsu, J. J. Hodgins, M. Marathe, et al., “Contribution of NK Cells to Immunotherapy Mediated by PD-1/PD-L1 Blockade,” Journal of Clinical Investigation 128, no. 10 (2018): 4654-4668.

[71] S. R. Gordon, R. L. Maute, B. W. Dulken, et al., “PD-1 Expression by Tumour-Associated Macrophages Inhibits Phagocytosis and Tumour Immunity,” Nature 545, no. 7655 (2017): 495-499.

[72] A. Mantovani, P. Allavena, F. Marchesi, and C. Garlanda, “Macrophages as Tools and Targets in Cancer Therapy,” Nature Reviews Drug Discovery 21, no. 11 (2022): 799-820.

[73] A. Kulikowska de Nałęcz, L. Ciszak, L. Usnarska-Zubkiewicz, et al., “Inappropriate Expression of PD-1 and CTLA-4 Checkpoints in Myeloma Patients Is More Pronounced at Diagnosis: Implications for Time to Progression and Response to Therapeutic Checkpoint Inhibitors,” International Journal of Molecular Sciences 24, no. 6 (2023): 5730.

[74] S. Najafi, J. Majidpoor, and K. Mortezaee, “The Impact of Microbiota on PD-1/PD-L1 Inhibitor Therapy Outcomes: A Focus on Solid Tumors,” Life Sciences 310 (2022): 121138.

[75] Q. Tang, Y. Chen, X. Li, et al., “The Role of PD-1/PD-L1 and Application of Immune-Checkpoint Inhibitors in Human Cancers,” Frontiers in Immunology 13 (2022): 964442.

[76] P. Pathria, T. L. Louis, and J. A. Varner, “Targeting Tumor-Associated Macrophages in Cancer,” Trends in Immunology 40, no. 4 (2019): 310-327.

[77] W. Xu, M. B. Atkins, and D. F. McDermott, “Checkpoint Inhibitor Immunotherapy in Kidney Cancer,” Nature Reviews Urology 17, no. 3 (2020): 137-150.

[78] E. K. Kleczko, D. T. Nguyen, K. H. Marsh, et al., “Immune Checkpoint Activity Regulates Polycystic Kidney Disease Progression,” JCI Insight 8, no. 12 (2023): e161318.

[79] M. Mayoux, A. Roller, V. Pulko, et al., “Dendritic Cells Dictate Responses to PD-L1 Blockade Cancer Immunotherapy,” Science Translational Medicine 12, no. 534 (2020): eaav7431.

[80] Y. Wang, J. Qiu, X. Qu, et al., “Accumulation of Dysfunctional Tumor-Infiltrating PD-1+ DCs Links PD-1/PD-L1 Blockade Immunotherapeutic Response in Cervical Cancer,” Oncoimmunology 11, no. 1 (2022): 2034257.

[81] X. Liu, A. Zhao, S. Xiao, et al., “PD-1: A Critical Player and Target for Immune Normalization,” Immunology 172, no. 2 (2024): 181-197.

[82] L. Zhao, S. Cheng, L. Fan, B. Zhang, and S. Xu, “TIM-3: An Update on Immunotherapy,” International Immunopharmacology 99 (2021): 107933.

[83] M. Das, C. Zhu, and V. K. Kuchroo, “Tim-3 and Its Role in Regulating Anti-Tumor Immunity,” Immunological Reviews 276, no. 1 (2017): 97-111.

[84] L. Monney, C. A. Sabatos, J. L. Gaglia, et al., “Th1-Specific Cell Surface Protein Tim-3 Regulates Macrophage Activation and Severity of an Autoimmune Disease,” Nature 415, no. 6871 (2002): 536-541.

[85] Y. Wolf, A. C. Anderson, and V. K. Kuchroo, “TIM3 Comes of Age as an Inhibitory Receptor,” Nature Reviews Immunology 20, no. 3 (2020): 173-185.

[86] I. P. da Silva, A. Gallois, S. Jimenez-Baranda, et al., “Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade,” Cancer Immunology Research 2, no. 5 (2014): 410-422.

[87] N. Sauer, N. Janicka, W. Szlasa, et al., “TIM-3 as a Promising Target for Cancer Immunotherapy in a Wide Range of Tumors,” Cancer Immunology, Immunotherapy 72, no. 11 (2023): 3405-3425.

[88] C. A. Sabatos, S. Chakravarti, E. Cha, et al., “Interaction of Tim-3 and Tim-3 Ligand Regulates T Helper Type 1 Responses and Induction of Peripheral Tolerance,” Nature Immunology 4, no. 11 (2003): 1102-1110.

[89] X. Du, Z. Wu, Y. Xu, et al., “Increased Tim-3 Expression Alleviates Liver Injury by Regulating Macrophage Activation in MCD-Induced NASH Mice,” Cellular & Molecular Immunology 16, no. 11 (2019): 878-886.

[90] J. H. Meyers, C. A. Sabatos, S. Chakravarti, and V. K. Kuchroo, “The TIM Gene Family Regulates Autoimmune and Allergic Diseases,” Trends in Molecular Medicine 11, no. 8 (2005): 362-369.

[91] L. Cai, Y. Li, J. Tan, L. Xu, and Y. Li, “Targeting LAG-3, TIM-3, and TIGIT for Cancer Immunotherapy,” Journal of Hematology & Oncology 16, no. 1 (2023): 101.

[92] A. L. Gomes de Morais, S. Cerdá, and M. de Miguel, “New Checkpoint Inhibitors on the Road: Targeting TIM-3 in Solid Tumors,” Current Oncology Reports 24, no. 5 (2022): 651-658.

[93] A. M. Zeidan, R. S. Komrokji, and A. M. Brunner, “TIM-3 Pathway Dysregulation and Targeting in Cancer,” Expert Review of Anticancer Therapy 21, no. 5 (2021): 523-534.

[94] Á. de Mingo Pulido, K. Hänggi, D. P. Celias, et al., “The Inhibitory Receptor TIM-3 Limits Activation of the cGAS-STING Pathway in Intra-Tumoral Dendritic Cells by Suppressing Extracellular DNA Uptake,” Immunity 54, no. 6 (2021): 1154-1167.e7.

[95] J. Lee, E. W. Su, C. Zhu, et al., “Phosphotyrosine-Dependent Coupling of Tim-3 to T-Cell Receptor Signaling Pathways,” Molecular and Cellular Biology 31, no. 19 (2011): 3963-3974.

[96] R. Yang and M. C. Hung, “The Role of T-Cell Immunoglobulin Mucin-3 and Its Ligand Galectin-9 in Antitumor Immunity and Cancer Immunotherapy,” Science China Life Sciences 60, no. 10 (2017): 1058-1064.

[97] S. Huang, D. Liu, J. Sun, et al., “Tim-3 Regulates Sepsis-Induced Immunosuppression by Inhibiting the NF-κB Signaling Pathway in CD4 T Cells,” Molecular Therapy 30, no. 3 (2022): 1227-1238.

[98] Y. Kikushige, “TIM-3 in Normal and Malignant Hematopoiesis: Structure, Function, and Signaling Pathways,” Cancer Science 112, no. 9 (2021): 3419-3426.

[99] S. Chiba, M. Baghdadi, H. Akiba, et al., “Tumor-Infiltrating DCs Suppress Nucleic Acid-Mediated Innate Immune Responses Through Interactions Between the Receptor TIM-3 and the Alarmin HMGB1,” Nature Immunology 13, no. 9 (2012): 832-842.

[100] H. Lin, B. Yang, and M. Teng, “T-Cell Immunoglobulin Mucin-3 as a Potential Inducer of the Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma,” Oncology Letters 14, no. 5 (2017): 5899-5905.

[101] Q. Shi, G. Li, S. Dou, et al., “Negative Regulation of RIG-I by Tim-3 Promotes H1N1 Infection,” Immunological Investigations 52, no. 1 (2023): 1-19.

[102] W. Zhu, Y. Tan, and F. Wang, “Tim-3: An Inhibitory Immune Checkpoint Is Associated With Maternal-Fetal Tolerance and Recurrent Spontaneous Abortion,” Clinical Immunology 245 (2022): 109185.

[103] Y. Jiang, H. Zhang, J. Wang, et al., “Exploiting RIG-I-Like Receptor Pathway for Cancer Immunotherapy,” Journal of Hematology & Oncology 16, no. 1 (2023): 8.

[104] C. Zhu, A. C. Anderson, A. Schubart, et al., “The Tim-3 Ligand Galectin-9 Negatively Regulates T Helper Type 1 Immunity,” Nature Immunology 6, no. 12 (2005): 1245-1252.

[105] O. Pagliano, R. M. Morrison, J. M. Chauvin, et al., “Tim-3 Mediates T Cell Trogocytosis to Limit Antitumor Immunity,” Journal of Clinical Investigation 132, no. 9 (2022): e152864.

[106] Y. Zhao, D. Chen, W. Wang, et al., “Significance of TIM-3 Expression in Resected Esophageal Squamous Cell Carcinoma,” Annals of Thoracic Surgery 109, no. 5 (2020): 1551-1557.

[107] C. Bailly, “Contribution of the TIM-3/Gal-9 Immune Checkpoint to Tropical Parasitic Diseases,” Acta Tropica 238 (2023): 106792.

[108] C. Santiago, A. Ballesteros, C. Tami, L. Martínez-Muñoz, G. G. Kaplan, and J. M. Casasnovas, “Structures of T Cell Immunoglobulin Mucin Receptors 1 and 2 Reveal Mechanisms for Regulation of Immune Responses by the TIM Receptor Family,” Immunity 26, no. 3 (2007): 299-310.

[109] Y. H. Huang, C. Zhu, Y. Kondo, et al., “CEACAM1 Regulates TIM-3-Mediated Tolerance and Exhaustion,” Nature 517, no. 7534 (2015): 386-390.

[110] L. Yuan, J. Tatineni, K. M. Mahoney, and G. J. Freeman, “VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy,” Trends in Immunology 42, no. 3 (2021): 209-227.

[111] L. Wang, R. Rubinstein, J. L. Lines, et al., “VISTA, a Novel Mouse Ig Superfamily Ligand That Negatively Regulates T Cell Responses,” Journal of Experimental Medicine 208, no. 3 (2011): 577-592.

[112] X. Huang, X. Zhang, E. Li, et al., “VISTA: An Immune Regulatory Protein Checking Tumor and Immune Cells in Cancer Immunotherapy,” Journal of Hematology & Oncology 13, no. 1 (2020): 83.

[113] A. S. Martin, M. Molloy, A. Ugolkov, et al., “VISTA Expression and Patient Selection for Immune-Based Anticancer Therapy,” Frontiers in Immunology 14 (2023): 1086102.

[114] M. A. ElTanbouly, Y. Zhao, E. Nowak, et al., “VISTA Is a Checkpoint Regulator for Naïve T Cell Quiescence and Peripheral Tolerance,” Science 367, no. 6475 (2020): eaay0524.

[115] J. Mo, L. Deng, K. Peng, et al., “Targeting STAT3-VISTA Axis to Suppress Tumor Aggression and Burden in Acute Myeloid Leukemia,” Journal of Hematology & Oncology 16, no. 1 (2023): 15.

[116] M. Zheng, Z. Zhang, L. Yu, et al., “Immune-Checkpoint Protein Vista in Allergic, Autoimmune Disease and Transplant Rejection,” Frontiers in Immunology 14 (2023): 1194421.

[117] M. Borggrewe, C. Grit, W. F. A. Den Dunnen, et al., “VISTA Expression by Microglia Decreases During Inflammation and Is Differentially Regulated in CNS Diseases,” GLIA 66, no. 12 (2018): 2645-2658.

[118] Y. Zhang, J. Hu, K. Ji, et al., “CD39 Inhibition and VISTA Blockade May Overcome Radiotherapy Resistance by Targeting Exhausted CD8+ T Cells and Immunosuppressive Myeloid Cells,” Cell Reports Medicine 4, no. 8 (2023): 101151.

[119] M. A. ElTanbouly, Y. Zhao, E. Schaafsma, et al., “VISTA: A Target to Manage the Innate Cytokine Storm,” Frontiers in Immunology 11 (2020): 595950.

[120] P. Chmiel, K. Gęca, A. Michalski, et al., “Vista of the Future: Novel Immunotherapy Based on the Human V-Set Immunoregulatory Receptor for Digestive System Tumors,” International Journal of Molecular Sciences 24, no. 12 (2023): 9945.

[121] M. A. ElTanbouly, W. Croteau, R. J. Noelle, and J. L. Lines, “VISTA: A Novel Immunotherapy Target for Normalizing Innate and Adaptive Immunity,” Seminars in Immunology 42 (2019): 101308.

[122] M. A. ElTanbouly, E. Schaafsma, R. J. Noelle, and J. L. Lines, “VISTA: Coming of Age as a Multi-Lineage Immune Checkpoint,” Clinical and Experimental Immunology 200, no. 2 (2020): 120-130.

[123] J. L. Lines, E. Pantazi, J. Mak, et al., “VISTA Is an Immune Checkpoint Molecule for Human T Cells,” Cancer Research 74, no. 7 (2014): 1924-1932.

[124] E. Schaafsma, W. Croteau, M. ElTanbouly, et al., “VISTA Targeting of T-Cell Quiescence and Myeloid Suppression Overcomes Adaptive Resistance,” Cancer Immunology Research 11, no. 1 (2023): 38-55.

[125] E. Im, D. Y. Sim, H. J. Lee, et al., “Immune Functions as a Ligand or a Receptor, Cancer Prognosis Potential, Clinical Implication of VISTA in Cancer Immunotherapy,” Seminars in Cancer Biology 86, no. Pt 2 (2022): 1066-1075.

[126] E. C. Nowak, J. L. Lines, F. S. Varn, et al., “Immunoregulatory Functions of VISTA,” Immunological Reviews 276, no. 1 (2017): 66-79.

[127] L. Wang, I. Le Mercier, J. Putra, et al., “Disruption of the Immune-Checkpoint VISTA Gene Imparts a Proinflammatory Phenotype With Predisposition to the Development of Autoimmunity,” Proceedings of the National Academy of Sciences 111, no. 41 (2014): 14846-14851.

[128] W. Xu, M. Hiếu, S. Malarkannan, and L. Wang, “The Structure, Expression, and Multifaceted Role of Immune-Checkpoint Protein VISTA as a Critical Regulator of Anti-Tumor Immunity, Autoimmunity, and Inflammation,” Cellular & Molecular Immunology 15, no. 5 (2018): 438-446.

[129] K. Zhang, A. Zakeri, T. Alban, et al., “VISTA Promotes the Metabolism and Differentiation of Myeloid-Derived Suppressor Cells by STAT3 and Polyamine-Dependent Mechanisms,” Cell Reports 43, no. 1 (2024): 113661.

[130] J. Wang, G. Wu, B. Manick, et al., “VSIG-3 as a Ligand of VISTA Inhibits Human T-Cell Function,” Immunology 156, no. 1 (2019): 74-85.

[131] X. Y. Tang, Y. L. Xiong, X. G. Shi, et al., “IGSF11 and VISTA: A Pair of Promising Immune Checkpoints in Tumor Immunotherapy,” Biomarker Research 10, no. 1 (2022): 49.

[132] K. Mulati, J. Hamanishi, N. Matsumura, et al., “VISTA Expressed in Tumour Cells Regulates T Cell Function,” British Journal of Cancer 120, no. 1 (2019): 115-127.

[133] R. J. Johnston, L. J. Su, J. Pinckney, et al., “VISTA Is an Acidic pH-Selective Ligand for PSGL-1,” Nature 574, no. 7779 (2019): 565-570.

[134] N. Shekari, D. Shanehbandi, T. Kazemi, H. Zarredar, B. Baradaran, and S. A. Jalali, “VISTA and Its Ligands: The Next Generation of Promising Therapeutic Targets in Immunotherapy,” Cancer Cell International 23, no. 1 (2023): 265.

[135] E. M. Muntjewerff, L. D. Meesters, and G. van den Bogaart, “Antigen Cross-Presentation by Macrophages,” Frontiers in Immunology 11 (2020): 1276.

[136] J. L. Guerriero, “Macrophages: Their Untold Story in T Cell Activation and Function,” International Review of Cell and Molecular Biology 342 (2019): 73-93.

[137] J. G. Cyster and C. D. C. Allen, “B Cell Responses: Cell Interaction Dynamics and Decisions,” Cell 177, no. 3 (2019): 524-540.

[138] X. Chen, Q. Lu, H. Zhou, et al., “A Membrane-Associated MHC-I Inhibitory Axis for Cancer Immune Evasion,” Cell 186, no. 18 (2023): 3903-3920.e21.

[139] K. Yamamoto, A. Venida, J. Yano, et al., “Autophagy Promotes Immune Evasion of Pancreatic Cancer by Degrading MHC-I,” Nature 581, no. 7806 (2020): 100-105.

[140] K. Dhatchinamoorthy, J. D. Colbert, and K. L. Rock, “Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation,” Frontiers in Immunology 12 (2021): 636568.

[141] X. Wu, T. Li, R. Jiang, X. Yang, H. Guo, and R. Yang, “Targeting MHC-I Molecules for Cancer: Function, Mechanism, and Therapeutic Prospects,” Molecular Cancer 22, no. 1 (2023): 194.

[142] The MHC Sequencing Consortium, “Complete Sequence and Gene Map of a Human Major Histocompatibility Complex,” Nature 401, no. 6756 (1999): 921-923.

[143] S. S. Gu, W. Zhang, X. Wang, et al., “Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade,” Cancer Discovery 11, no. 6 (2021): 1524-1541.

[144] M. L. Burr, C. E. Sparbier, K. L. Chan, et al., “An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer,” Cancer Cell 36, no. 4 (2019): 385-401.e8.

[145] J. Trowsdale, “Genomic Structure and Function in the MHC,” Trends in Genetics 9, no. 4 (1993): 117-122.

[146] J. Zhao, S. Zhong, X. Niu, J. Jiang, R. Zhang, and Q. Li, “The MHC Class I-LILRB1 Signalling Axis as a Promising Target in Cancer Therapy,” Scandinavian Journal of Immunology 90, no. 5 (2019): e12804.

[147] B. C. Taylor and J. M. Balko, “Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response,” Frontiers in Immunology 13 (2022): 844866.

[148] J. Wang, Q. Lu, X. Chen, and I. Aifantis, “Targeting MHC-I Inhibitory Pathways for Cancer Immunotherapy,” Trends in Immunology 45, no. 3 (2024): 177-187.

[149] U. M. Demel, M. Böger, S. Yousefian, et al., “Activated SUMOylation Restricts MHC Class I Antigen Presentation to Confer Immune Evasion in Cancer,” Journal of Clinical Investigation 132, no. 9 (2022): e152383.

[150] R. W. Lentz, M. D. Colton, S. S. Mitra, and W. A. Messersmith, “Innate Immune Checkpoint Inhibitors: The Next Breakthrough in Medical Oncology?,” Molecular Cancer Therapeutics 20, no. 6 (2021): 961-974.

[151] C. L. Dulberger, C. P. McMurtrey, A. Hölzemer, et al., “Human Leukocyte Antigen F Presents Peptides and Regulates Immunity Through Interactions With NK Cell Receptors,” Immunity 46, no. 6 (2017): 1018-1029.e7.

[152] T. Zeller, I. A. Münnich, R. Windisch, et al., “Perspectives of Targeting LILRB1 in Innate and Adaptive Immune Checkpoint Therapy of Cancer,” Frontiers in Immunology 14 (2023): 1240275.

[153] Z. Hu, Q. Zhang, Z. He, X. Jia, W. Zhang, and X. Cao, “MHC1/LILRB1 Axis as an Innate Immune Checkpoint for Cancer Therapy,” Frontiers in Immunology 15 (2024): 1421092.

[154] W. van der Touw, H. M. Chen, P. Y. Pan, and S. H. Chen, “LILRB Receptor-Mediated Regulation of Myeloid Cell Maturation and Function,” Cancer Immunology, Immunotherapy 66, no. 8 (2017): 1079-1087.

[155] N. T. Young, E. C. P. Waller, R. Patel, A. Roghanian, J. M. Austyn, and J. Trowsdale, “The Inhibitory Receptor LILRB1 Modulates the Differentiation and Regulatory Potential of Human Dendritic Cells,” Blood 111, no. 6 (2008): 3090-3096.

[156] X. Kang, J. Kim, M. Deng, et al., “Inhibitory Leukocyte Immunoglobulin-Like Receptors: Immune Checkpoint Proteins and Tumor Sustaining Factors,” Cell Cycle 15, no. 1 (2016): 25-40.

[157] A. Naji, C. Menier, G. Maki, E. D. Carosella, and N. Rouas-Freiss, “Neoplastic B-Cell Growth Is Impaired by HLA-G/ILT2 Interaction,” Leukemia 26, no. 8 (2012): 1889-1892.

[158] T. Sinthuwiwat, S. Buranapraditkun, W. Kamolvisit, et al., “A LILRB1 Variant With a Decreased Ability to Phosphorylate SHP-1 Leads to Autoimmune Diseases,” Scientific Reports 12, no. 1 (2022): 15420.

[159] P. Bruhns, F. Vély, O. Malbec, W. H. Fridman, E. Vivier, and M. Daëron, “Molecular Basis of the Recruitment of the SH2 Domain-Containing Inositol 5-Phosphatases SHIP1 and SHIP2 by FcγRIIB,” Journal of Biological Chemistry 275, no. 48 (2000): 37357-37364.

[160] E. Bernit, E. Jean, B. Marlot, et al., “HLA-F and LILRB1 Genetic Polymorphisms Associated With Alloimmunisation in Sickle Cell Disease,” International Journal of Molecular Sciences 24, no. 17 (2023): 13591.

[161] J. Middelburg, S. Ghaffari, T. A. W. Schoufour, et al., “The MHC-E Peptide Ligands for Checkpoint CD94/NKG2A Are Governed by Inflammatory Signals, Whereas LILRB1/2 Receptors Are Peptide Indifferent,” Cell Reports 42, no. 12 (2023): 113516.

[162] M. Daëron, S. Jaeger, L. Du Pasquier, and E. Vivier, “Immunoreceptor Tyrosine-Based Inhibition Motifs: A Quest in the Past and Future,” Immunological Reviews 224 (2008): 11-43.

[163] D. Baía, J. Pou, D. Jones, et al., “Interaction of the LILRB1 Inhibitory Receptor With HLA Class Ia Dimers,” European Journal of Immunology 46, no. 7 (2016): 1681-1690.

[164] M. Xian, Q. Wang, L. Xiao, et al., “Leukocyte Immunoglobulin-Like Receptor B1 (LILRB1) Protects Human Multiple Myeloma Cells From Ferroptosis by Maintaining Cholesterol Homeostasis,” Nature Communications 15, no. 1 (2024): 5767.

[165] X. Liu, H. Kwon, Z. Li, and Y. Fu, “Is CD47 an Innate Immune Checkpoint for Tumor Evasion?,” Journal of Hematology & Oncology 10, no. 1 (2017): 12.

[166] S. B. Willingham, J. P. Volkmer, A. J. Gentles, et al., “The CD47-Signal Regulatory Protein Alpha (SIRPa) Interaction Is a Therapeutic Target for Human Solid Tumors,” Proceedings of the National Academy of Sciences 109, no. 17 (2012): 6662-6667.

[167] Y. Li, H. Zhou, P. Liu, et al., “SHP2 Deneddylation Mediates Tumor Immunosuppression in Colon Cancer via the CD47/SIRPα Axis,” Journal of Clinical Investigation 133, no. 4 (2023): e162870.

[168] M. E. W. Logtenberg, F. A. Scheeren, and T. N. Schumacher, “The CD47-SIRPα Immune Checkpoint,” Immunity 52, no. 5 (2020): 742-752.

[169] X. Jia, B. Yan, X. Tian, et al., “CD47/SIRPα Pathway Mediates Cancer Immune Escape and Immunotherapy,” International Journal of Biological Sciences 17, no. 13 (2021): 3281-3287.

[170] G. Fenalti, N. Villanueva, M. Griffith, et al., “Structure of the Human Marker of Self 5-Transmembrane Receptor CD47,” Nature Communications 12, no. 1 (2021): 5218.

[171] K. Weiskopf, “Cancer Immunotherapy Targeting the CD47/SIRPα Axis,” European Journal of Cancer 76 (2017): 100-109.

[172] L. Ma, M. Zhu, J. Gai, et al., “Preclinical Development of a Novel CD47 Nanobody With Less Toxicity and Enhanced Anti-Cancer Therapeutic Potential,” Journal of Nanobiotechnology 18, no. 1 (2020): 12.

[173] H. L. Matlung, K. Szilagyi, N. A. Barclay, and T. K. van den Berg, “The CD47-SIRPα Signaling Axis as an Innate Immune Checkpoint in Cancer,” Immunological Reviews 276, no. 1 (2017): 145-164.

[174] A. Veillette and J. Chen, “SIRPα-CD47 Immune Checkpoint Blockade in Anticancer Therapy,” Trends in Immunology 39, no. 3 (2018): 173-184.

[175] Z. Li, Y. Li, J. Gao, et al., “The Role of CD47-SIRPα Immune Checkpoint in Tumor Immune Evasion and Innate Immunotherapy,” Life Sciences 273 (2021): 119150.

[176] Y. Nishiga, A. P. Drainas, M. Baron, et al., “Radiotherapy in Combination With CD47 Blockade Elicits a Macrophage-Mediated Abscopal Effect,” Nature Cancer 3, no. 11 (2022): 1351-1366.

[177] T. C. Kuo, A. Chen, O. Harrabi, et al., “Targeting the Myeloid Checkpoint Receptor SIRPα Potentiates Innate and Adaptive Immune Responses to Promote Anti-Tumor Activity,” Journal of Hematology & Oncology 13, no. 1 (2020): 160.

[178] A. van Duijn, S. H. Van der Burg, and F. A. Scheeren, “CD47/SIRPα Axis: Bridging Innate and Adaptive Immunity,” Journal for Immunotherapy of Cancer 10, no. 7 (2022): e004589.

[179] P. A. Oldenborg, H. D. Gresham, and F. P. Lindberg, “Cd47-Signal Regulatory Protein α (Sirpα) Regulates Fcγ and Complement Receptor-Mediated Phagocytosis,” Journal of Experimental Medicine 193, no. 7 (2001): 855-862.

[180] S. M. G. Hayat, V. Bianconi, M. Pirro, M. R. Jaafari, M. Hatamipour, and A. Sahebkar, “CD47: Role in the Immune System and Application to Cancer Therapy,” Cellular Oncology 43, no. 1 (2020): 19-30.

[181] C. M. Schürch, M. A. Roelli, S. Forster, et al., “Targeting CD47 in Anaplastic Thyroid Carcinoma Enhances Tumor Phagocytosis by Macrophages and Is a Promising Therapeutic Strategy,” Thyroid 29, no. 7 (2019): 979-992.

[182] Y. Murata, Y. Saito, T. Kotani, and T. Matozaki, “Blockade of CD47 or SIRPα: A New Cancer Immunotherapy,” Expert Opinion on Therapeutic Targets 24, no. 10 (2020): 945-951.

[183] A. R. Jalil, M. P. Tobin, and D. E. Discher, “Suppressing or Enhancing Macrophage Engulfment Through the Use of CD47 and Related Peptides,” Bioconjugate Chemistry 33, no. 11 (2022): 1989-1995.

[184] R. K. Narla, H. Modi, D. Bauer, et al., “Modulation of CD47-SIRPα Innate Immune Checkpoint Axis With Fc-Function Detuned Anti-CD47 Therapeutic Antibody,” Cancer Immunology, Immunotherapy 71, no. 2 (2022): 473-489.

[185] M. E. W. Logtenberg, J. H. M. Jansen, M. Raaben, et al., “Glutaminyl Cyclase Is an Enzymatic Modifier of the CD47-SIRPα Axis and a Target for Cancer Immunotherapy,” Nature Medicine 25, no. 4 (2019): 612-619.

[186] T. Deuse, X. Hu, S. Agbor-Enoh, et al., “The SIRPα-CD47 Immune Checkpoint in NK Cells,” Journal of Experimental Medicine 218, no. 3 (2021): e20200839.

[187] T. Matozaki, Y. Murata, H. Okazawa, and H. Ohnishi, “Functions and Molecular Mechanisms of the CD47-SIRPα Signalling Pathway,” Trends in Cell Biology 19, no. 2 (2009): 72-80.

[188] H. Shi, X. Wang, F. Li, et al., “CD47-SIRPα Axis Blockade in NASH Promotes Necroptotic Hepatocyte Clearance by Liver Macrophages and Decreases Hepatic Fibrosis,” Science Translational Medicine 14, no. 672 (2022): eabp8309.

[189] L. W. Treffers, T. Ten Broeke, T. Rösner, et al., “IgA-Mediated Killing of Tumor Cells by Neutrophils Is Enhanced by CD47-SIRPα Checkpoint Inhibition,” Cancer Immunology Research 8, no. 1 (2020): 120-130.

[190] K. Weiskopf, N. S. Jahchan, P. J. Schnorr, et al., “CD47-Blocking Immunotherapies Stimulate Macrophage-Mediated Destruction of Small-Cell Lung Cancer,” Journal of Clinical Investigation 126, no. 7 (2016): 2610-2620.

[191] S. H. Chen, P. K. Dominik, J. Stanfield, et al., “Dual Checkpoint Blockade of CD47 and PD-L1 Using an Affinity-Tuned Bispecific Antibody Maximizes Antitumor Immunity,” Journal for Immunotherapy of Cancer 9, no. 10 (2021): e003464.

[192] P. Altevogt, M. Sammar, L. Hüser, and G. Kristiansen, “Novel Insights Into the Function of CD24: A Driving Force in Cancer,” International Journal of Cancer 148, no. 3 (2021): 546-559.

[193] H. Deng, G. Wang, S. Zhao, et al., “New Hope for Tumor Immunotherapy: The Macrophage-Related “Do Not Eat Me” Signaling Pathway,” Frontiers in Pharmacology 14 (2023): 1228962.

[194] K. Kleinmanns, K. Bischof, S. Anandan, et al., “CD24-Targeted Fluorescence Imaging in Patient-Derived Xenograft Models of High-Grade Serous Ovarian Carcinoma,” EBioMedicine 56 (2020): 102782.

[195] Y. Liu and P. Zheng, “CD24-Siglec Interactions in Inflammatory Diseases,” Frontiers in Immunology 14 (2023): 1174789.

[196] Y. Yang, G. Zhu, L. Yang, and Y. Yang, “Targeting CD24 as a Novel Immunotherapy for Solid Cancers,” Cell Communication and Signaling 21, no. 1 (2023): 312.

[197] Y. Gu, G. Zhou, X. Tang, F. Shen, J. Ding, and K. Hua, “The Biological Roles of CD24 in Ovarian Cancer: Old Story, but New Tales,” Frontiers in Immunology 14 (2023): 1183285.

[198] V. Tarhriz, M. Bandehpour, S. Dastmalchi, E. Ouladsahebmadarek, H. Zarredar, and S. Eyvazi, “Overview of CD24 as a New Molecular Marker in Ovarian Cancer,” Journal of Cellular Physiology 234, no. 3 (2019): 2134-2142.

[199] X. Li, W. Tian, Z. Jiang, Y. Song, X. Leng, and J. Yu, “Targeting CD24/Siglec-10 Signal Pathway for Cancer Immunotherapy: Recent Advances and Future Directions,” Cancer Immunology, Immunotherapy 73, no. 2 (2024): 31.

[200] G. Y. Chen, N. K. Brown, P. Zheng, and Y. Liu, “Siglec-G/10 in Self-Nonself Discrimination of Innate and Adaptive Immunity,” Glycobiology 24, no. 9 (2014): 800-806.

[201] A. A. Barkal, R. E. Brewer, M. Markovic, et al., “CD24 Signalling Through Macrophage Siglec-10 Is a Target for Cancer Immunotherapy,” Nature 572, no. 7769 (2019): 392-396.

[202] W. Shen, P. Shi, Q. Dong, et al., “Discovery of a Novel Dual-Targeting D-Peptide to Block CD24/Siglec-10 and PD-1/PD-L1 Interaction and Synergize With Radiotherapy for Cancer Immunotherapy,” Journal for Immunotherapy of Cancer 11, no. 6 (2023): e007068.

[203] X. Wang, M. Liu, J. Zhang, et al., “CD24-Siglec Axis Is an Innate Immune Checkpoint Against Metaflammation and Metabolic Disorder,” Cell Metabolism 34, no. 8 (2022): 1088-1103.e6.

[204] Y. Liu, G. Y. Chen, and P. Zheng, “CD24-Siglec G/10 Discriminates Danger - From Pathogen-Associated Molecular Patterns,” Trends in Immunology 30, no. 12 (2009): 557-561.

[205] K. Wang, A. Yu, K. Liu, et al., “Nano-LYTACs for Degradation of Membrane Proteins and Inhibition of CD24/Siglec-10 Signaling Pathway,” Advanced Science 10, no. 13 (2023): e2300288.

[206] S. S. Yin and F. H. Gao, “Molecular Mechanism of Tumor Cell Immune Escape Mediated by CD24/Siglec-10,” Frontiers in Immunology 11 (2020): 1324.

[207] G. Y. Chen, J. Tang, P. Zheng, and Y. Liu, “CD24 and Siglec-10 Selectively Repress Tissue Damage-Induced Immune Responses,” Science 323, no. 5922 (2009): 1722-1725.

[208] L. Yang, A. Li, Q. Lei, and Y. Zhang, “Tumor-Intrinsic Signaling Pathways: Key Roles in the Regulation of the Immunosuppressive Tumor Microenvironment,” Journal of Hematology & Oncology 12, no. 1 (2019): 125.

[209] N. Li, P. Zheng, and Y. Liu, “The CD24-Siglec G Axis Protects Mice Against Cuprizone-Induced Oligodendrocyte Loss: Targeting Danger Signal for Neuroprotection,” Cellular & Molecular Immunology 15, no. 1 (2018): 79-81.

[210] C. A. Bradley, “CD24 - A Novel ‘Don't Eat Me’ Signal,” Nature Reviews Cancer 19, no. 10 (2019): 541.

[211] M. J. Kiel, Ö. H. Yilmaz, T. Iwashita, O. H. Yilmaz, C. Terhorst, and S. J. Morrison, “SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells,” Cell 121, no. 7 (2005): 1109-1121.

[212] P. Engel, M. J. Eck, and C. Terhorst, “The SAP and SLAM Families in Immune Responses and X-Linked Lymphoproliferative Disease,” Nature Reviews Immunology 3, no. 10 (2003): 813-821.

[213] M. Ishibashi, R. Morita, and H. Tamura, “Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma,” Cancers 13, no. 2 (2021): 279.

[214] J. L. Cannons, S. G. Tangye, and P. L. Schwartzberg, “SLAM Family Receptors and SAP Adaptors in Immunity,” Annual Review of Immunology 29 (2011): 665-705.

[215] D. Li, W. Xiong, Y. Wang, et al., “SLAMF3 and SLAMF4 Are Immune Checkpoints That Constrain Macrophage Phagocytosis of Hematopoietic Tumors,” Science Immunology 7, no. 67 (2022): 5501.

[216] C. Detre, M. Keszei, X. Romero, G. C. Tsokos, and C. Terhorst, “SLAM Family Receptors and the SLAM-Associated Protein (SAP) Modulate T Cell Functions,” Seminars in Immunopathology 32, no. 2 (2010): 157-171.

[217] R. Bhat, P. Eissmann, J. Endt, S. Hoffmann, and C. Watzl, “Fine-Tuning of Immune Responses by SLAM-Related Receptors,” Journal of Leukocyte Biology 79, no. 3 (2006): 417-424.

[218] J. Chen, M. C. Zhong, H. Guo, et al., “SLAMF7 Is Critical for Phagocytosis of Haematopoietic Tumour Cells via Mac-1 Integrin,” Nature 544, no. 7651 (2017): 493-497.

[219] B. H. Y. Yeung, A. Y. S. Law, and C. K. C. Wong, “Evolution and Roles of Stanniocalcin,” Molecular and Cellular Endocrinology 349, no. 2 (2012): 272-280.

[220] K. Sundell, T. Björnsson, H. Itoh, and H. Kawauchi, “Chum Salmon (Oncorhynchus keta) Stanniocalcin Inhibitis In Vitro Intestinal Calcium Uptake in Atlantic Cod (Gadus morhua),” Journal of Comparative Physiology B 162, no. 6 (1992): 489-495.

[221] P. Juhanson, K. Rull, T. Kikas, et al., “Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators,” Journal of Clinical Endocrinology & Metabolism 101, no. 12 (2016): 4799-4807.

[222] M. Kikuchi, Y. Nakano, Y. Nambo, et al., “Production of Calcium Maintenance Factor Stanniocalcin-1 (STC1) by the Equine Endometrium During the Early Pregnant Period,” Journal of Reproduction and Development 57, no. 2 (2011): 203-211.

[223] K. K. S. Chan, C. O. N. Leung, C. C. L. Wong, et al., “Secretory Stanniocalcin 1 Promotes Metastasis of Hepatocellular Carcinoma Through Activation of JNK Signaling Pathway,” Cancer Letters 403 (2017): 330-338.

[224] C. C. Leung and C. K. Wong, “Effects of STC1 Overexpression on Tumorigenicity and Metabolism of Hepatocellular Carcinoma,” Oncotarget 9, no. 6 (2018): 6852-6861.

[225] J. Sakata, T. Sasayama, K. Tanaka, et al., “MicroRNA Regulating Stanniocalcin-1 Is a Metastasis and Dissemination Promoting Factor in Glioblastoma,” Journal of Neuro-Oncology 142, no. 2 (2019): 241-251.

[226] H. Lin, I. Kryczek, S. Li, et al., “Stanniocalcin 1 Is a Phagocytosis Checkpoint Driving Tumor Immune Resistance,” Cancer Cell 39, no. 4 (2021): 480-493.e6.

[227] A. Liu, Y. Li, S. Lu, C. Cai, F. Zou, and X. Meng, “Stanniocalcin 1 Promotes Lung Metastasis of Breast Cancer by Enhancing EGFR-ERK-S100A4 Signaling,” Cell Death & Disease 14, no. 7 (2023): 395.

[228] Y. Wang, Z. Qi, M. Zhou, et al., “Stanniocalcin-1 Promotes Cell Proliferation, Chemoresistance and Metastasis in Hypoxic Gastric Cancer Cells via Bcl-2,” Oncology Reports 41, no. 3 (2019): 1998-2008.

[229] D. Sheikh-Hamad, “Mammalian Stanniocalcin-1 Activates Mitochondrial Antioxidant Pathways: New Paradigms for Regulation of Macrophages and Endothelium,” American Journal of Physiology-Renal Physiology 298, no. 2 (2010): F248-F254.

[230] J. Kanellis, R. Bick, G. Garcia, et al., “Stanniocalcin-1, an Inhibitor of Macrophage Chemotaxis and Chemokinesis,” American Journal of Physiology-Renal Physiology 286, no. 2 (2004): F356-F362.

[231] A. D. Joshi, “New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2,” Frontiers in Endocrinology 11 (2020): 172.

[232] K. M. Baecher and M. L. Ford, “Intersection of FcγRIIB, the Microbiome, and Checkpoint Inhibitors in Antitumor Immunity,” Cancer Immunology, Immunotherapy 70, no. 12 (2021): 3397-3404.

[233] P. M. Hogarth, “Fc Receptors: Introduction,” Immunological Reviews 268, no. 1 (2015): 1-5.

[234] P. M. Hogarth and G. A. Pietersz, “Fc Receptor-Targeted Therapies for the Treatment of Inflammation, Cancer and Beyond,” Nature Reviews Drug Discovery 11, no. 4 (2012): 311-331.

[235] G. van Tetering, M. Evers, C. Chan, M. Stip, and J. Leusen, “Fc Engineering Strategies to Advance IgA Antibodies as Therapeutic Agents,” Antibodies 9, no. 4 (2020): 70.

[236] A. B. Morris, C. R. Farley, D. F. Pinelli, et al., “Signaling Through the Inhibitory Fc Receptor FcγRIIB Induces CD8(+) T Cell Apoptosis to Limit T Cell Immunity,” Immunity 52, no. 1 (2020): 136-150.e6.

[237] T. Takai, “Fc Receptors and Their Role in Immune Regulation and Autoimmunity,” Journal of Clinical Immunology 25, no. 1 (2005): 1-18.

[238] C. R. Farley, A. B. Morris, M. Tariq, et al., “FcγRIIB Is a T Cell Checkpoint in Antitumor Immunity,” JCI Insight 6, no. 4 (2021): e135623.

[239] T. Takai, “Roles of Fc Receptors in Autoimmunity,” Nature Reviews Immunology 2, no. 8 (2002): 580-592.

[240] N. S. Wilson, B. Yang, A. Yang, et al., “An Fcγ Receptor-Dependent Mechanism Drives Antibody-Mediated Target-Receptor Signaling in Cancer Cells,” Cancer Cell 19, no. 1 (2011): 101-113.

[241] I. Teige, L. Mårtensson, and B. L. Frendéus, “Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB,” Frontiers in Immunology 10 (2019): 481.

[242] T. Castro-Dopico and M. R. Clatworthy, “IgG and Fcγ Receptors in Intestinal Immunity and Inflammation,” Frontiers in Immunology 10 (2019): 805.

[243] S. Ben Mkaddem, M. Benhamou, and R. C. Monteiro, “Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools,” Frontiers in Immunology 10 (2019): 811.

[244] M. C. Veri, S. Gorlatov, H. Li, et al., “Monoclonal Antibodies Capable of Discriminating the Human Inhibitory Fcγ-Receptor IIB (CD32B) From the Activating Fcγ-Receptor IIA (CD32A): Biochemical, Biological and Functional Characterization,” Immunology 121, no. 3 (2007): 392-404.

[245] S. Angiari, T. Donnarumma, B. Rossi, et al., “TIM-1 Glycoprotein Binds the Adhesion Receptor P-Selectin and Mediates T Cell Trafficking During Inflammation and Autoimmunity,” Immunity 40, no. 4 (2014): 542-553.

[246] X. Tian, X. Zheng, and D. Tian, “B-Cell Immune Checkpoint TIM-1: A Potential Target for Tumour Immunotherapy,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 389.

[247] G. Oliveira and C. J. Wu, “Dynamics and Specificities of T Cells in Cancer Immunotherapy,” Nature Reviews Cancer 23, no. 5 (2023): 295-316.

[248] L. Sun, Y. Su, A. Jiao, X. Wang, and B. Zhang, “T Cells in Health and Disease,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 235.

[249] H. Raskov, A. Orhan, J. P. Christensen, and I. Gögenur, “Cytotoxic CD8(+) T Cells in Cancer and Cancer Immunotherapy,” British Journal of Cancer 124, no. 2 (2021): 359-367.

[250] T. J. Laskowski, A. Biederstädt, and K. Rezvani, “Natural Killer Cells in Antitumour Adoptive Cell Immunotherapy,” Nature Reviews Cancer 22, no. 10 (2022): 557-575.

[251] Y. Liu and P. Zheng, “Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy,” Trends in Pharmacological Sciences 41, no. 1 (2020): 4-12.

[252] S. Agarwal, M. A. Aznar, A. J. Rech, et al., “Deletion of the Inhibitory Co-Receptor CTLA-4 Enhances and Invigorates Chimeric Antigen Receptor T Cells,” Immunity 56, no. 10 (2023): 2388-2407.e9.

[253] M. Ramos-Casals, J. R. Brahmer, M. K. Callahan, et al., “Immune-Related Adverse Events of Checkpoint Inhibitors,” Nature Reviews Disease Primers 6, no. 1 (2020): 38.

[254] A. Arra, M. Pech, H. Fu, et al., “Immune-Checkpoint Blockade of CTLA-4 (CD152) in Antigen-Specific Human T-Cell Responses Differs Profoundly Between Neonates, Children, and Adults,” Oncoimmunology 10, no. 1 (2021): 1938475.

[255] M. Babamohamadi, N. Mohammadi, E. Faryadi, et al., “Anti-CTLA-4 Nanobody as a Promising Approach in Cancer Immunotherapy,” Cell Death & Disease 15, no. 1 (2024): 17.

[256] H. Lingel and M. C. Brunner-Weinzierl, “CTLA-4 (CD152): A Versatile Receptor for Immune-Based Therapy,” Seminars in Immunology 42 (2019): 101298.

[257] J. F. Brunet, F. Denizot, M. F. Luciani, et al., “A New Member of the Immunoglobulin Superfamily—CTLA-4,” Nature 328, no. 6127 (1987): 267-270.

[258] B. Lo and U. M. Abdel-Motal, “Lessons From CTLA-4 Deficiency and Checkpoint Inhibition,” Current Opinion in Immunology 49 (2017): 14-19.

[259] P. Régnier, A. Le Joncour, A. Maciejewski-Duval, et al., “CTLA-4 Pathway Is Instrumental in Giant Cell Arteritis,” Circulation Research 133, no. 4 (2023): 298-312.

[260] J. Brzostek, N. R. J. Gascoigne, and V. Rybakin, “Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition,” Frontiers in Immunology 7 (2016): 24.

[261] L. S. K. Walker and D. M. Sansom, “Confusing Signals: Recent Progress in CTLA-4 Biology,” Trends in Immunology 36, no. 2 (2015): 63-70.

[262] D. A. Ostrov, W. Shi, J. C. D. Schwartz, S. C. Almo, and S. G. Nathenson, “Structure of Murine CTLA-4 and Its Role in Modulating T Cell Responsiveness,” Science 290, no. 5492 (2000): 816-819.

[263] C. Genova, C. Dellepiane, P. Carrega, et al., “Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade,” Frontiers in Immunology 12 (2021): 799455.

[264] Y. Pico de Coaña, A. Choudhury, and R. Kiessling, “Checkpoint Blockade for Cancer Therapy: Revitalizing a Suppressed Immune System,” Trends in Molecular Medicine 21, no. 8 (2015): 482-491.

[265] F. Maszyna, H. Hoff, D. Kunkel, A. Radbruch, and M. C. Brunner-Weinzierl, “Diversity of Clonal T Cell Proliferation Is Mediated by Differential Expression of CD152 (CTLA-4) on the Cell Surface of Activated Individual T Lymphocytes,” Journal of Immunology 171, no. 7 (2003): 3459-3466.

[266] B. Rowshanravan, N. Halliday, and D. M. Sansom, “CTLA-4: A Moving Target in Immunotherapy,” Blood 131, no. 1 (2018): 58-67.

[267] J. G. Egen and J. P. Allison, “Cytotoxic T Lymphocyte Antigen-4 Accumulation in the Immunological Synapse Is Regulated by TCR Signal Strength,” Immunity 16, no. 1 (2002): 23-35.

[268] P. Pandiyan, D. Gärtner, O. Soezeri, A. Radbruch, K. Schulze-Osthoff, and M. C. Brunner-Weinzierl, “CD152 (CTLA-4) Determines the Unequal Resistance of Th1 and Th2 Cells Against Activation-Induced Cell Death by a Mechanism Requiring PI3 Kinase Function,” Journal of Experimental Medicine 199, no. 6 (2004): 831-842.

[269] K. Knieke, H. Hoff, F. Maszyna, et al., “CD152 (CTLA-4) Determines CD4 T Cell Migration In Vitro and In Vivo,” PLoS One 4, no. 5 (2009): e5702.

[270] S. V. Podlesnykh, K. E. Abramova, A. Gordeeva, A. I. Khlebnikov, and A. I. Chapoval, “Peptide Blocking CTLA-4 and B7-1 Interaction,” Molecules 26, no. 2 (2021): 253.

[271] A. Kennedy, E. Waters, B. Rowshanravan, et al., “Differences in CD80 and CD86 Transendocytosis Reveal CD86 as a Key Target for CTLA-4 Immune Regulation,” Nature Immunology 23, no. 9 (2022): 1365-1378.

[272] Y. Zhang, X. Du, M. Liu, et al., “Hijacking Antibody-Induced CTLA-4 Lysosomal Degradation for Safer and More Effective Cancer Immunotherapy,” Cell Research 29, no. 8 (2019): 609-627.

[273] L. Karabon, A. Partyka, L. Ciszak, et al., “Abnormal Expression of BTLA and CTLA-4 Immune Checkpoint Molecules in Chronic Lymphocytic Leukemia Patients,” Journal of Immunology Research 2020 (2020): 6545921.

[274] G. R. Khosravi, S. Mostafavi, S. Bastan, N. Ebrahimi, R. S. Gharibvand, and N. Eskandari, “Immunologic Tumor Microenvironment Modulators for Turning Cold Tumors Hot,” Cancer Communications 44, no. 5 (2024): 521-553.

[275] M. Fathi, S. M. Razavi, M. Sojoodi, et al., “Targeting the CTLA-4/B7 Axes in Glioblastoma: Preclinical Evidence and Clinical Interventions,” Expert Opinion on Therapeutic Targets 26, no. 11 (2022): 949-961.

[276] S. Ben, Q. Zhu, S. Chen, et al., “Genetic Variations in the CTLA-4 Immune Checkpoint Pathway Are Associated With Colon Cancer Risk, Prognosis, and Immune Infiltration via Regulation of IQCB1 Expression,” Archives of Toxicology 95, no. 6 (2021): 2053-2063.

[277] K. M. Lee, E. Chuang, M. Griffin, et al., “Molecular Basis of T Cell Inactivation by CTLA-4,” Science 282, no. 5397 (1998): 2263-2266.

[278] L. E. M. Marengère, P. Waterhouse, G. S. Duncan, H. W. Mittrücker, G. S. Feng, and T. W. Mak, “Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association With CTLA-4,” Science 272, no. 5265 (1996): 1170-1173.

[279] Á. D. Apol, A. A. Winckelmann, R. B. Duus, J. Bukh, and N. Weis, “The Role of CTLA-4 in T Cell Exhaustion in Chronic Hepatitis B Virus Infection,” Viruses 15, no. 5 (2023): 1141.

[280] F. Ghorbaninezhad, J. Masoumi, M. Bakhshivand, et al., “CTLA-4 Silencing in Dendritic Cells Loaded With Colorectal Cancer Cell Lysate Improves Autologous T Cell Responses In Vitro,” Frontiers in Immunology 13 (2022): 931316.

[281] G. Kroemer and L. Zitvogel, “Immune Checkpoint Inhibitors,” Journal of Experimental Medicine 218, no. 3 (2021): e20201979.

[282] S. J. Wang, S. K. Dougan, and M. Dougan, “Immune Mechanisms of Toxicity From Checkpoint Inhibitors,” Trends in Cancer 9, no. 7 (2023): 543-553.

[283] C. Zhang, J. Chen, Q. Song, et al., “Comprehensive Analysis of CTLA-4 in the Tumor Immune Microenvironment of 33 Cancer Types,” International Immunopharmacology 85 (2020): 106633.

[284] A. Tanaka and S. Sakaguchi, “Regulatory T Cells in Cancer Immunotherapy,” Cell Research 27, no. 1 (2017): 109-118.

[285] A. Selvakumar, U. Steffens, and B. Dupont, “NK Cell Receptor Gene of the KIR Family With Two IG Domains but Highest Homology to KIR Receptors With Three IG Domains,” Tissue Antigens 48, no. 4, pt. 1 (1996): 285-295.

[286] M. Uhrberg, “The KIR Gene Family: Life in the Fast Lane of Evolution,” European Journal of Immunology 35, no. 1 (2005): 10-15.

[287] D. Middleton and F. Gonzelez, “The Extensive Polymorphism of KIR Genes,” Immunology 129, no. 1 (2010): 8-19.

[288] K. C. Hsu, S. Chida, D. E. Geraghty, and B. Dupont, “The Killer Cell Immunoglobulin-Like Receptor (KIR) Genomic Region: Gene-Order, Haplotypes and Allelic Polymorphism,” Immunological Reviews 190 (2002): 40-52.

[289] V. Béziat, H. G. Hilton, P. J. Norman, and J. A. Traherne, “Deciphering the Killer-Cell Immunoglobulin-Like Receptor System at Super-Resolution for Natural Killer and T-Cell Biology,” Immunology 150, no. 3 (2017): 248-264.

[290] S. Sivori, P. Vacca, G. Del Zotto, E. Munari, M. C. Mingari, and L. Moretta, “Human NK Cells: Surface Receptors, Inhibitory Checkpoints, and Translational Applications,” Cellular & Molecular Immunology 16, no. 5 (2019): 430-441.

[291] D. Pende, M. Falco, M. Vitale, et al., “Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation,” Frontiers in Immunology 10 (2019): 1179.

[292] S. G. E. Marsh, P. Parham, B. Dupont, et al., “Killer-Cell Immunoglobulin-Like Receptor (KIR) Nomenclature Report, 2002,” Human Immunology 64, no. 6 (2003): 648-654.

[293] J. Robinson, J. A. Halliwell, J. D. Hayhurst, P. Flicek, P. Parham, and S. G. E. Marsh, “The IPD and IMGT/HLA Database: Allele Variant Databases,” Nucleic Acids Research 43 (2015): D423-D431.

[294] H. G. Hilton, P. J. Norman, N. Nemat-Gorgani, et al., “Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter-Gatherer Population,” PLoS Genetics 11, no. 8 (2015): e1005439.

[295] H. G. Hilton, L. A. Guethlein, A. Goyos, et al., “Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes,” Journal of Immunology 195, no. 7 (2015): 3160-3170.

[296] A. K. Moesta, P. J. Norman, M. Yawata, N. Yawata, M. Gleimer, and P. Parham, “Synergistic Polymorphism at Two Positions Distal to the Ligand-Binding Site Makes KIR2DL2 a Stronger Receptor for HLA-C Than KIR2DL3,” Journal of Immunology 180, no. 6 (2008): 3969-3979.

[297] H. G. Hilton and P. Parham, “Missing or Altered Self: Human NK Cell Receptors That Recognize HLA-C,” Immunogenetics 69, no. 8/9 (2017): 567-579.

[298] M. Stern, L. Ruggeri, M. Capanni, A. Mancusi, and A. Velardi, “Human Leukocyte Antigens A23, A24, and A32 but Not A25 Are Ligands for KIR3DL1,” Blood 112, no. 3 (2008): 708-710.

[299] G. M. O'Connor, K. J. Guinan, R. T. Cunningham, D. Middleton, P. Parham, and C. M. Gardiner, “Functional Polymorphism of the KIR3DL1/S1 Receptor on Human NK Cells,” Journal of Immunology 178, no. 1 (2007): 235-241.

[300] R. Biassoni, C. Cantoni, M. Falco, et al., “The Human Leukocyte Antigen (HLA)-C-Specific “Activatory” or “Inhibitory” Natural Killer Cell Receptors Display Highly Homologous Extracellular Domains but Differ in Their Transmembrane and Intracytoplasmic Portions,” Journal of Experimental Medicine 183, no. 2 (1996): 645-650.

[301] A. Moretta, S. Sivori, M. Vitale, et al., “Existence of Both Inhibitory (p58) and Activatory (p50) Receptors for HLA-C Molecules in Human Natural Killer Cells,” Journal of Experimental Medicine 182, no. 3 (1995): 875-884.

[302] A. D'Andrea, C. Chang, K. Franz-Bacon, T. McClanahan, J. H. Phillips, and L. L. Lanier, “Molecular Cloning of NKB1. A Natural Killer Cell Receptor for HLA-B Allotypes,” Journal of Immunology 155, no. 5 (1995): 2306-2310.

[303] M. Khan, S. Arooj, and H. Wang, “NK Cell-Based Immune Checkpoint Inhibition,” Frontiers in Immunology 11 (2020): 167.

[304] M. G. Morvan and L. L. Lanier, “NK Cells and Cancer: You Can Teach Innate Cells New Tricks,” Nature Reviews Cancer 16, no. 1 (2016): 7-19.

[305] D. N. Burshtyn, A. M. Scharenberg, N. Wagtmann, et al., “Recruitment of Tyrosine Phosphatase HCP by the Killer Cell Inhibitory Receptor,” Immunity 4, no. 1 (1996): 77-85.

[306] M. Li, P. Xia, Y. Du, et al., “T-Cell Immunoglobulin and ITIM Domain (TIGIT) Receptor/Poliovirus Receptor (PVR) Ligand Engagement Suppresses Interferon-γ Production of Natural Killer Cells via β-Arrestin 2-Mediated Negative Signaling,” Journal of Biological Chemistry 289, no. 25 (2014): 17647-17657.

[307] C. J. Nirschl and C. G. Drake, “Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy,” Clinical Cancer Research 19, no. 18 (2013): 4917-4924.

[308] F. Borrego, J. Kabat, D. K. Kim, et al., “Structure and Function of Major Histocompatibility Complex (MHC) Class I Specific Receptors Expressed on Human Natural Killer (NK) Cells,” Molecular Immunology 38, no. 9 (2002): 637-660.

[309] X. Liu, J. Song, H. Zhang, et al., “Immune Checkpoint HLA-E:CD94-NKG2A Mediates Evasion of Circulating Tumor Cells From NK Cell Surveillance,” Cancer Cell 41, no. 2 (2023): 272-287.e9.

[310] B. D. Huisman, N. Guan, T. Rückert, et al., “High-Throughput Characterization of HLA-E-Presented CD94/NKG2x Ligands Reveals Peptides Which Modulate NK Cell Activation,” Nature Communications 14, no. 1 (2023): 4809.

[311] M. López-Botet, A. Muntasell, and C. Vilches, “The CD94/NKG2C+ NK-Cell Subset on the Edge of Innate and Adaptive Immunity to Human Cytomegalovirus Infection,” Seminars in Immunology 26, no. 2 (2014): 145-151.

[312] M. Iwaszko, J. Świerkot, K. Kolossa, S. Jeka, P. Wiland, and K. Bogunia-Kubik, “Influence of CD94 and NKG2A Variants on Susceptibility to Rheumatoid Arthritis and Efficacy of Anti-TNF Treatment,” Joint, Bone, Spine 83, no. 1 (2016): 75-79.

[313] E. J. Petrie, C. S. Clements, J. Lin, et al., “CD94-NKG2A Recognition of Human Leukocyte Antigen (HLA)-E Bound to an HLA Class I Leader Sequence,” Journal of Experimental Medicine 205, no. 3 (2008): 725-735.

[314] E. Le Dréan, F. Vély, L. Olcese, et al., “Inhibition of Antigen-Induced T Cell Response and Antibody-Induced NK Cell Cytotoxicity by NKG2A: Association of NKG2A With SHP-1 and SHP-2 Protein-Tyrosine Phosphatases,” European Journal of Immunology 28, no. 1 (1998): 264-276.

[315] S. Sarantopoulos, L. Lu, and H. Cantor, “Qa-1 Restriction of CD8+ Suppressor T Cells,” Journal of Clinical Investigation 114, no. 9 (2004): 1218-1221.

[316] J. M. Moser, J. Gibbs, P. E. Jensen, and A. E. Lukacher, “CD94-NKG2A Receptors Regulate Antiviral CD8(+) T Cell Responses,” Nature Immunology 3, no. 2 (2002): 189-195.

[317] I. Algarra, A. García-Lora, T. Cabrera, F. Ruiz-Cabello, and F. Garrido, “The Selection of Tumor Variants With Altered Expression of Classical and Nonclassical MHC Class I Molecules: Implications for Tumor Immune Escape,” Cancer Immunology, Immunotherapy 53, no. 10 (2004): 904-910.

[318] N. van Montfoort, L. Borst, M. J. Korrer, et al., “NKG2A Blockade Potentiates CD8 T Cell Immunity Induced by Cancer Vaccines,” Cell 175, no. 7 (2018): 1744-1755.e15.

[319] E. Levy, M. Bianchini, E. Von Euw, et al., “Human Leukocyte Antigen-E Protein Is Overexpressed in Primary Human Colorectal Cancer,” International Journal of Oncology 32, no. 3 (2008): 633-641.

[320] H. Zheng, R. Lu, S. Xie, et al., “Human Leukocyte Antigen-E Alleles and Expression in Patients With Serous Ovarian Cancer,” Cancer Science 106, no. 5 (2015): 522-528.

[321] L. Kren, P. Fabian, O. Slaby, et al., “Multifunctional Immune-Modulatory Protein HLA-E Identified in Classical Hodgkin Lymphoma: Possible Implications,” Pathology - Research and Practice 208, no. 1 (2012): 45-49.

[322] F. Triebel, S. Jitsukawa, E. Baixeras, et al., “LAG-3, a Novel Lymphocyte Activation Gene Closely Related to CD4,” Journal of Experimental Medicine 171, no. 5 (1990): 1393-1405.

[323] L. Chocarro, E. Blanco, M. Zuazo, et al., “Understanding LAG-3 Signaling,” International Journal of Molecular Sciences 22, no. 10 (2021): 5282.

[324] F. Y. Kreidieh and H. A. Tawbi, “The Introduction of LAG-3 Checkpoint Blockade in Melanoma: Immunotherapy Landscape Beyond PD-1 and CTLA-4 Inhibition,” Therapeutic Advances in Medical Oncology 15 (2023): 17588359231186027.

[325] J. L. Huo, Y. T. Wang, W. J. Fu, N. Lu, and Z. S. Liu, “The Promising Immune Checkpoint LAG-3 in Cancer Immunotherapy: From Basic Research to Clinical Application,” Frontiers in Immunology 13 (2022): 956090.

[326] B. Huard, R. Mastrangeli, P. Prigent, et al., “Characterization of the Major Histocompatibility Complex Class II Binding Site on LAG-3 Protein,” Proceedings of the National Academy of Sciences 94, no. 11 (1997): 5744-5749.

[327] J. Wang, R. Meijers, Y. Xiong, et al., “Crystal Structure of the Human CD4 N-Terminal Two-Domain Fragment Complexed to a Class II MHC Molecule,” Proceedings of the National Academy of Sciences 98, no. 19 (2001): 10799-10804.

[328] J. Tian, Y. Liu, T. Zhang, L. Yue, Y. Xiao, and C. Guo, “LAG-3 Is a Promising Inhibitory Immune Checkpoint for Antitumor Immunotherapy,” Expert Review of Anticancer Therapy 22, no. 3 (2022): 289-296.

[329] T. Maruhashi, D. Sugiura, I. Okazaki, et al., “Binding of LAG-3 to Stable Peptide-MHC Class II Limits T Cell Function and Suppresses Autoimmunity and Anti-Cancer Immunity,” Immunity 55, no. 5 (2022): 912-924.e8.

[330] T. Maruhashi, D. Sugiura, I. Okazaki, and T. Okazaki, “LAG-3: From Molecular Functions to Clinical Applications,” Journal for Immunotherapy of Cancer 8, no. 2 (2020): e001014.

[331] K. P. Burke, D. G. Patterson, D. Liang, and A. H. Sharpe, “Immune Checkpoint Receptors in Autoimmunity,” Current Opinion in Immunology 80 (2023): 102283.

[332] B. Huard, P. Prigent, M. Tournier, D. Bruniquel, and F. Triebel, “CD4/Major Histocompatibility Complex Class II Interaction Analyzed With CD4- and Lymphocyte Activation Gene-3 (LAG-3)-Ig Fusion Proteins,” European Journal of Immunology 25, no. 9 (1995): 2718-2721.

[333] Q. Lecocq, M. Keyaerts, N. Devoogdt, and K. Breckpot, “The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time's a Charm,” International Journal of Molecular Sciences 22, no. 1 (2020): 75.

[334] S. Andreae, S. Buisson, and F. Triebel, “MHC Class II Signal Transduction in Human Dendritic Cells Induced by a Natural Ligand, the LAG-3 Protein (CD223),” Blood 102, no. 6 (2003): 2130-2137.

[335] B. Huard, M. Tournier, T. Hercend, F. Triebel, and F. Faure, “Lymphocyte-Activation Gene 3/Major Histocompatibility Complex Class II Interaction Modulates the Antigenic Response of CD4+ T Lymphocytes,” European Journal of Immunology 24, no. 12 (1994): 3216-3221.

[336] B. Huard, P. Prigent, F. Pagès, D. Bruniquel, and F. Triebel, “T Cell Major Histocompatibility Complex Class II Molecules Down-Regulate CD4+ T Cell Clone Responses Following LAG-3 Binding,” European Journal of Immunology 26, no. 5 (1996): 1180-1186.

[337] P. Hemon, F. Jean-Louis, K. Ramgolam, et al., “MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis,” Journal of Immunology 186, no. 9 (2011): 5173-5183.

[338] E. Sung, M. Ko, J. Won, et al., “LAG-3xPD-L1 Bispecific Antibody Potentiates Antitumor Responses of T Cells Through Dendritic Cell Activation,” Molecular Therapy 30, no. 8 (2022): 2800-2816.

[339] M. Li, Y. M. Feng, and S. Q. Fang, “Overexpression of Ezrin and Galectin-3 as Predictors of Poor Prognosis of Cervical Cancer,” Brazilian Journal of Medical and Biological Research 50, no. 4 (2017): e5356.

[340] J. Dumic, S. Dabelic, and M. Flögel, “Galectin-3: An Open-Ended Story,” Biochimica et Biophysica Acta (BBA) - General Subjects 1760, no. 4 (2006): 616-635.

[341] W. Liu, L. Tang, G. Zhang, et al., “Characterization of a Novel C-Type Lectin-Like Gene, LSECtin,” Journal of Biological Chemistry 279, no. 18 (2004): 18748-18758.

[342] H. Harjunpää and C. Guillerey, “TIGIT as an Emerging Immune Checkpoint,” Clinical and Experimental Immunology 200, no. 2 (2020): 108-119.

[343] J. M. Chauvin and H. M. Zarour, “TIGIT in Cancer Immunotherapy,” Journal for Immunotherapy of Cancer 8, no. 2 (2020): e000957.

[344] W. Tang, J. Chen, T. Ji, and X. Cong, “TIGIT, a Novel Immune Checkpoint Therapy for Melanoma,” Cell Death & Disease 14, no. 7 (2023): 466.

[345] X. Yu, K. Harden, L. C Gonzalez, et al., “The Surface Protein TIGIT Suppresses T Cell Activation by Promoting the Generation of Mature Immunoregulatory Dendritic Cells,” Nature Immunology 10, no. 1 (2009): 48-57.

[346] E. Y. Chiang and I. Mellman, “TIGIT-CD226-PVR Axis: Advancing Immune Checkpoint Blockade for Cancer Immunotherapy,” Journal for Immunotherapy of Cancer 10, no. 4 (2022): e004711.

[347] S. D. Levin, D. W. Taft, C. S. Brandt, et al., “Vstm3 Is a Member of the CD28 Family and an Important Modulator of T-Cell Function,” European Journal of Immunology 41, no. 4 (2011): 902-915.

[348] J. Wienke, L. L. Visser, W. M. Kholosy, et al., “Integrative Analysis of Neuroblastoma by Single-Cell RNA Sequencing Identifies the NECTIN2-TIGIT Axis as a Target for Immunotherapy,” Cancer Cell 42, no. 2 (2024): 283-300.e8.

[349] J. Yeo, M. Ko, D. H. Lee, Y. Park, and H. Jin, “TIGIT/CD226 Axis Regulates Anti-Tumor Immunity,” Pharmaceuticals 14, no. 3 (2021): 200.

[350] S. Noel, K. Lee, S. Gharaie, et al., “Immune Checkpoint Molecule TIGIT Regulates Kidney T Cell Functions and Contributes to AKI,” Journal of the American Society of Nephrology 34, no. 5 (2023): 755-771.

[351] R. J. Johnston, L. Comps-Agrar, J. Hackney, et al., “The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8(+) T Cell Effector Function,” Cancer Cell 26, no. 6 (2014): 923-937.

[352] L. Liu, X. You, S. Han, Y. Sun, J. Zhang, and Y. Zhang, “CD155/TIGIT, a Novel Immune Checkpoint in Human Cancers (Review),” Oncology Reports 45, no. 3 (2021): 835-845.

[353] T. Annese, R. Tamma, and D. Ribatti, “Update in TIGIT Immune-Checkpoint Role in Cancer,” Frontiers in Oncology 12 (2022): 871085.

[354] Z. Ge, M. P. Peppelenbosch, D. Sprengers, and J. Kwekkeboom, “TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer,” Frontiers in Immunology 12 (2021): 699895.

[355] J. D. Worboys, K. N. Vowell, R. K. Hare, et al., “TIGIT Can Inhibit T Cell Activation via Ligation-Induced Nanoclusters, Independent of CD226 Co-Stimulation,” Nature Communications 14, no. 1 (2023): 5016.

[356] N. Jantz-Naeem, R. Böttcher-Loschinski, K. Borucki, et al., “TIGIT Signaling and Its Influence on T Cell Metabolism and Immune Cell Function in the Tumor Microenvironment,” Frontiers in Oncology 13 (2023): 1060112.

[357] J. Godfrey, X. Chen, N. Sunseri, et al., “TIGIT Is a Key Inhibitory Checkpoint Receptor in Lymphoma,” Journal for Immunotherapy of Cancer 11, no. 6 (2023): e006582.

[358] J. Fourcade, Z. Sun, J. M. Chauvin, et al., “CD226 Opposes TIGIT to Disrupt Tregs in Melanoma,” JCI Insight 3, no. 14 (2018): e121157.

[359] N. Joller, E. Lozano, P. R. Burkett, et al., “Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses,” Immunity 40, no. 4 (2014): 569-581.

[360] S. Liu, H. Zhang, M. Li, et al., “Recruitment of Grb2 and SHIP1 by the ITT-Like Motif of TIGIT Suppresses Granule Polarization and Cytotoxicity of NK Cells,” Cell Death & Differentiation 20, no. 3 (2013): 456-464.

[361] H. Pearce, W. Croft, S. M. Nicol, et al., “Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade,” Cancer Immunology Research 11, no. 4 (2023): 435-449.

[362] B. Luo, Y. Sun, Q. Zhan, et al., “Combining TIGIT Blockade With IL-15 Stimulation Is a Promising Immunotherapy Strategy for Lung Adenocarcinoma,” Clinical and Translational Medicine 14, no. 1 (2024): e1553.

[363] F. Alvarez Calderon, B. H. Kang, O. Kyrysyuk, et al., “Targeting of the CD161 Inhibitory Receptor Enhances T-Cell-Mediated Immunity Against Hematological Malignancies,” Blood 143, no. 12 (2024): 1124-1138.

[364] C. Sordo-Bahamonde, S. Lorenzo-Herrero, R. Granda-Díaz, et al., “Beyond the Anti-PD-1/PD-L1 Era: Promising Role of the BTLA/HVEM Axis as a Future Target for Cancer Immunotherapy,” Molecular Cancer 22, no. 1 (2023): 142.

[365] C. Li, L. Zhang, Q. Jin, H. Jiang, and C. Wu, “CD39 (ENTPD1) in Tumors: A Potential Therapeutic Target and Prognostic Biomarker,” Biomarkers in Medicine 17, no. 12 (2023): 563-576.

[366] X. Liao, Y. Guo, Y. He, Y. Xiao, J. Li, and R. Liu, “Metabolic Enzymes Function as Epigenetic Modulators: A Trojan Horse for Chromatin Regulation and Gene Expression,” Pharmacological Research 173 (2021): 105834.

[367] Y. Xiao, H. Zhou, L. Jiang, R. Liu, and Q. Chen, “Epigenetic Regulation of Ion Channels in the Sense of Taste,” Pharmacological Research 172 (2021): 105760.

[368] A. Kallingal, M. Olszewski, N. Maciejewska, W. Brankiewicz, and M. Baginski, “Cancer Immune Escape: The Role of Antigen Presentation Machinery,” Journal of Cancer Research and Clinical Oncology 149, no. 10 (2023): 8131-8141.

[369] Y. Godiyal, D. Maheshwari, H. Taniguchi, et al., “Role of PD-1/PD-L1 Signaling Axis in Oncogenesis and Its Targeting by Bioactive Natural Compounds for Cancer Immunotherapy,” Military Medical Research 11, no. 1 (2024): 82.

[370] A. Chennamadhavuni, L. Abushahin, N. Jin, C. J. Presley, and A. Manne, “Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors,” Frontiers in Immunology 13 (2022): 779691.

[371] L. Xia, Y. Liu, and Y. Wang, “PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions,” supplement, Oncologist 24, no. S1 (2019): S31-S41.

[372] S. Najafi, J. Majidpoor, and K. Mortezaee, “Extracellular Vesicle-Based Drug Delivery in Cancer Immunotherapy,” Drug Delivery and Translational Research 13, no. 11 (2023): 2790-2806.

[373] C. Yang, B. R. Xia, Z. C. Zhang, Y. J. Zhang, G. Lou, and W. L. Jin, “Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant,” Frontiers in Immunology 11 (2020): 577869.

[374] A. Snyder, V. Makarov, T. Merghoub, et al., “Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma,” New England Journal of Medicine 371, no. 23 (2014): 2189-2199.

[375] J. Kang, C. Zhang, and W. Z. Zhong, “Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer: State of the Art,” Cancer Communications 41, no. 4 (2021): 287-302.

[376] L. Moreland, G. Bate, and P. Kirkpatrick, “Abatacept,” Nature Reviews Drug Discovery 5, no. 3 (2006): 185-186.

[377] S. J. Keam, “Tremelimumab: First Approval,” Drugs 83, no. 1 (2023): 93-102.

[378] F. Cameron, G. Whiteside, and C. Perry, “Ipilimumab: First Global Approval,” Drugs 71, no. 8 (2011): 1093-1104.

[379] P. Archdeacon, C. Dixon, O. Belen, R. Albrecht, and J. Meyer, “Summary of the US FDA Approval of Belatacept,” American Journal of Transplantation 12, no. 3 (2012): 554-562.

[380] S. J. Keam, “Cadonilimab: First Approval,” Drugs 82, no. 12 (2022): 1333-1339.

[381] S. J. Keam, “Toripalimab: First Global Approval,” Drugs 79, no. 5 (2019): 573-578.

[382] A. Lee and S. J. Keam, “Tislelizumab: First Approval,” Drugs 80, no. 6 (2020): 617-624.

[383] R. M. Poole, “Pembrolizumab: First Global Approval,” Drugs 74, no. 16 (2014): 1973-1981.

[384] S. M. Hoy, “Sintilimab: First Global Approval,” Drugs 79, no. 3 (2019): 341-346.

[385] A. Markham and S. Duggan, “Cemiplimab: First Global Approval,” Drugs 78, no. 17 (2018): 1841-1846.

[386] C. Kang, “Retifanlimab: First Approval,” Drugs 83, no. 8 (2023): 731-737.

[387] A. Markham and S. J. Keam, “Camrelizumab: First Global Approval,” Drugs 79, no. 12 (2019): 1355-1361.

[388] A. Lee, “Serplulimab: First Approval,” Drugs 82, no. 10 (2022): 1137-1141.

[389] J. Zuo, L. Wu, X. Li, et al., “Efficacy and Safety of Enlonstobart (SG001), a PD-1 Inhibitor in Patients With PD-L1 Positive Recurrent/Metastatic Cervical Cancer: A Multicenter, Single-Arm, Open-Label, Phase II Study,” supplement, Journal of Clinical Oncology 42, no. S16 (2024): 5526.

[390] S. Dhillon, “Penpulimab: First Approval,” Drugs 81, no. 18 (2021): 2159-2166.

[391] A. Markham, “Dostarlimab: First Approval,” Drugs 81, no. 10 (2021): 1213-1219.

[392] A. Markham, “Zimberelimab: First Approval,” Drugs 81, no. 17 (2021): 2063-2068.

[393] H. Kaplon and J. M. Reichert, “Antibodies to Watch in 2021,” mAbs 13, no. 1 (2021): 1860476.

[394] S. Tjulandin, L. Demidov, V. Moiseyenko, et al., “Novel PD-1 Inhibitor Prolgolimab: Expanding Non-Resectable/Metastatic Melanoma Therapy Choice,” European Journal of Cancer 149 (2021): 222-232.

[395] S. Dhillon, “Pucotenlimab: First Approval,” Drugs 82, no. 15 (2022): 1557-1564.

[396] J. Paik, “Nivolumab Plus Relatlimab: First Approval,” Drugs 82, no. 8 (2022): 925-931.

[397] S. Dhillon, “Ivonescimab: First Approval,” Drugs 84, no. 9 (2024): 1135-1142.

[398] Y. Y. Syed, “Durvalumab: First Global Approval,” Drugs 77, no. 12 (2017): 1369-1376.

[399] S. Dhillon and S. Duggan, “Sugemalimab: First Approval,” Drugs 82, no. 5 (2022): 593-599.

[400] A. Markham, “Atezolizumab: First Global Approval,” Drugs 76, no. 12 (2016): 1227-1232.

[401] E. S. Kim, “Avelumab: First Global Approval,” Drugs 77, no. 8 (2017): 929-937.

[402] A. Markham, “Envafolimab: First Approval,” Drugs 82, no. 2 (2022): 235-240.

[403] H. E. Marei, A. Hasan, G. Pozzoli, and C. Cenciarelli, “Cancer Immunotherapy With Immune Checkpoint Inhibitors (ICIs): Potential, Mechanisms of Resistance, and Strategies for Reinvigorating T Cell Responsiveness When Resistance Is Acquired,” Cancer Cell International 23, no. 1 (2023): 64.

[404] E. De Martin, J. M. Michot, O. Rosmorduc, C. Guettier, and D. Samuel, “Liver Toxicity as a Limiting Factor to the Increasing Use of Immune Checkpoint Inhibitors,” JHEP Reports 2, no. 6 (2020): 100170.

[405] Y. Xu, P. Li, Y. Liu, et al., “Epi-Immunotherapy for Cancers: Rationales of Epi-Drugs in Combination With Immunotherapy and Advances in Clinical Trials,” Cancer Communications 42, no. 6 (2022): 493-516.

[406] S. Jeong, E. Park, H. D. Kim, et al., “Novel Anti-4-1BB×PD-L1 Bispecific Antibody Augments Anti-Tumor Immunity Through Tumor-Directed T-Cell Activation and Checkpoint Blockade,” Journal for Immunotherapy of Cancer 9, no. 7 (2021): e002428.

[407] Y. Y. Janjigian, A. Kawazoe, P. Yañez, et al., “The KEYNOTE-811 Trial of Dual PD-1 and HER2 Blockade in HER2-Positive Gastric Cancer,” Nature 600, no. 7890 (2021): 727-730.

[408] Y. Kondo, J. Akahira, T. Morosawa, et al., “Anti-Nuclear Antibody and a Granuloma Could Be Biomarkers for iCIs-Related Hepatitis by Anti-PD-1 Treatment,” Scientific Reports 12, no. 1 (2022): 3669.

[409] Y. Naito, S. Koyama, K. Masuhiro, et al., “Tumor-Derived Semaphorin 4A Improves PD-1-Blocking Antibody Efficacy by Enhancing CD8(+) T Cell Cytotoxicity and Proliferation,” Science Advances 9, no. 20 (2023): eade0718.

[410] W. Hugo, J. M. Zaretsky, L. Sun, et al., “Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma,” Cell 165, no. 1 (2016): 35-44.

[411] S. Upadhaya, S. T. Neftelino, J. P. Hodge, C. Oliva, J. R. Campbell, and J. X. Yu, “Combinations Take Centre Stage in PD1/PDL1 Inhibitor Clinical Trials,” Nature Reviews Drug Discovery 20, no. 3 (2021): 168-169.

[412] F. Peyraud, J. P. Guégan, D. Bodet, et al., “Circulating L-Arginine Predicts the Survival of Cancer Patients Treated With Immune Checkpoint Inhibitors,” Annals of Oncology 33, no. 10 (2022): 1041-1051.

[413] Z. Z. Yu, Y. Y. Liu, W. Zhu, et al., “ANXA1-Derived Peptide for Targeting PD-L1 Degradation Inhibits Tumor Immune Evasion in Multiple Cancers,” Journal for Immunotherapy of Cancer 11, no. 3 (2023): e006345.

[414] L. D. S. Johnson, S. Banerjee, O. Kruglov, et al., “Targeting CD47 in Sézary Syndrome With SIRPαFc,” Blood Advances 3, no. 7 (2019): 1145-1153.

[415] J. Theruvath, M. Menard, B. A. H. Smith, et al., “Anti-GD2 Synergizes With CD47 Blockade to Mediate Tumor Eradication,” Nature Medicine 28, no. 2 (2022): 333-344.

[416] S. Gholamin, S. S. Mitra, A. H. Feroze, et al., “Disrupting the CD47-SIRPα Anti-Phagocytic Axis by a Humanized Anti-CD47 Antibody Is an Efficacious Treatment for Malignant Pediatric Brain Tumors,” Science Translational Medicine 9, no. 381 (2017): eaaf2968.

[417] J. Liu, L. Wang, F. Zhao, et al., “Pre-Clinical Development of a Humanized Anti-CD47 Antibody With Anti-Cancer Therapeutic Potential,” PLoS One 10, no. 9 (2015): e0137345.

[418] W. Leung, R. Handgretinger, R. Iyengar, V. Turner, M. S. Holladay, and G. A. Hale, “Inhibitory KIR-HLA Receptor-Ligand Mismatch in Autologous Haematopoietic Stem Cell Transplantation for Solid Tumour and Lymphoma,” British Journal of Cancer 97, no. 4 (2007): 539-542.

[419] K. Beksac, M. Beksac, K. Dalva, E. Karaagaoglu, and M. B. Tirnaksiz, “Impact of “Killer Immunoglobulin-Like Receptor/Ligand” Genotypes on Outcome Following Surgery Among Patients With Colorectal Cancer: Activating KIRs Are Associated With Long-Term Disease Free Survival,” PLoS One 10, no. 7 (2015): e0132526.

[420] Y. He, P. A. Bunn, C. Zhou, and D. Chan, “KIR 2D (L1, L3, L4, S4) and KIR 3DL1 Protein Expression in Non-Small Cell Lung Cancer,” Oncotarget 7, no. 50 (2016): 82104-82111.

[421] V. Varbanova, E. Naumova, and A. Mihaylova, “Killer-Cell Immunoglobulin-Like Receptor Genes and Ligands and Their Role in Hematologic Malignancies,” Cancer Immunology, Immunotherapy 65, no. 4 (2016): 427-440.

[422] F. F. Yalniz, N. Daver, K. Rezvani, et al., “A Pilot Trial of Lirilumab With or Without Azacitidine for Patients With Myelodysplastic Syndrome,” Clinical Lymphoma Myeloma and Leukemia 18, no. 10 (2018): 658-663.e2.

[423] D. M. Benson, , A. D. Cohen, S. Jagannath, et al., “A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients With Relapsed/Refractory Multiple Myeloma,” Clinical Cancer Research 21, no. 18 (2015): 4055-4061.

[424] C. W. McMahon, A. J. Zajac, A. M. Jamieson, et al., “Viral and Bacterial Infections Induce Expression of Multiple NK Cell Receptors in Responding CD8(+) T Cells,” Journal of Immunology 169, no. 3 (2002): 1444-1452.

[425] M. Zheng, Y. Gao, G. Wang, et al., “Functional Exhaustion of Antiviral Lymphocytes in COVID-19 Patients,” Cellular & Molecular Immunology 17, no. 5 (2020): 533-535.

[426] A. Yaqinuddin and J. Kashir, “Innate Immunity in COVID-19 Patients Mediated by NKG2A Receptors, and Potential Treatment Using Monalizumab, Cholroquine, and Antiviral Agents,” Medical Hypotheses 140 (2020): 109777.

[427] P. Sharma and J. P. Allison, “The Future of Immune Checkpoint Therapy,” Science 348, no. 6230 (2015): 56-61.

[428] L. Galluzzi, A. Buqué, O. Kepp, L. Zitvogel, and G. Kroemer, “Immunogenic Cell Death in Cancer and Infectious Disease,” Nature Reviews Immunology 17, no. 2 (2017): 97-111.

[429] P. S. Hegde, J. J. Wallin, and C. Mancao, “Predictive Markers of Anti-VEGF and Emerging Role of Angiogenesis Inhibitors as Immunotherapeutics,” Seminars in Cancer Biology 52, no. Pt 2 (2018): 117-124.

[430] M. C. Garassino, S. Gadgeel, G. Speranza, et al., “Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study,” Journal of Clinical Oncology 41, no. 11 (2023): 1992-1998.

[431] L. Gandhi, D. Rodríguez-Abreu, S. Gadgeel, et al., “Pembrolizumab Plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer,” New England Journal of Medicine 378, no. 22 (2018): 2078-2092.

[432] J. Larkin, V. Chiarion-Sileni, R. Gonzalez, et al., “Five-Year Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma,” New England Journal of Medicine 381, no. 16 (2019): 1535-1546.

[433] P. Schmid, S. Adams, H. S. Rugo, et al., “Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer,” New England Journal of Medicine 379, no. 22 (2018): 2108-2121.

[434] A. Ribas, D. Lawrence, V. Atkinson, et al., “Publisher Correction: Combined BRAF and MEK Inhibition With PD-1 Blockade Immunotherapy in BRAF-Mutant Melanoma,” Nature Medicine 25, no. 8 (2019): 1319.

[435] J. B. A. G. Haanen, F. Carbonnel, C. Robert, et al., “Management of Toxicities From Immunotherapy: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up,” supplement, Annals of Oncology 28, no. S4 (2017): iv119-iv142.

[436] S. M. Blum, S. J. Rouhani, and R. J. Sullivan, “Effects of Immune-Related Adverse Events (irAEs) and Their Treatment on Antitumor Immune Responses,” Immunological Reviews 318, no. 1 (2023): 167-178.

[437] B. Shankar, J. Zhang, A. R. Naqash, et al., “Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer,” JAMA Oncology 6, no. 12 (2020): 1952-1956.

[438] G. Kroemer, C. Galassi, L. Zitvogel, and L. Galluzzi, “Immunogenic Cell Stress and Death,” Nature Immunology 23, no. 4 (2022): 487-500.

[439] L. Galluzzi, E. Guilbaud, D. Schmidt, G. Kroemer, and F. M. Marincola, “Targeting Immunogenic Cell Stress and Death for Cancer Therapy,” Nature Reviews Drug Discovery 23, no. 6 (2024): 445-460.

[440] D. V. Krysko, A. D. Garg, A. Kaczmarek, O. Krysko, P. Agostinis, and P. Vandenabeele, “Immunogenic Cell Death and DAMPs in Cancer Therapy,” Nature Reviews Cancer 12, no. 12 (2012): 860-875.

[441] R. Liang, D. Ding, Y. Li, et al., “HDACi Combination Therapy With IDO1i Remodels the Tumor Microenvironment and Boosts Antitumor Efficacy in Colorectal Cancer With Microsatellite Stability,” Journal of Nanobiotechnology 22, no. 1 (2024): 753.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm - Oncology published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).