Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations

Tianying Hu , Jianxue Zhai , Zhanda Yang , Jiajia Peng , Chuxuan Wang , Xinyao Liu , Yawen Li , Jiaqi Yao , Fengxi Chen , Haixia Li , Taixue An , Zongcai Liu , Haifang Wang

MedComm ›› 2025, Vol. 6 ›› Issue (6) : e70231

PDF
MedComm ›› 2025, Vol. 6 ›› Issue (6) :e70231 DOI: 10.1002/mco2.70231
REVIEW

Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations

Author information +
History +
PDF

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that expand aberrantly in cancer and exhibit potent immunosuppressive properties. They contribute to tumor progression through both immunological and nonimmunological mechanisms. Immunologically, MDSCs suppress antitumor responses by inhibiting effector cells such as T cells and NK cells, facilitating immune evasion. Nonimmunologically, they promote tumor growth and metastasis through processes such as the epithelial‒mesenchymal transition, angiogenesis, and premetastatic niche formation. MDSC accumulation is closely linked to accelerated tumor progression, including resistance to both immunotherapies and conventional treatments, making these cells critical therapeutic targets. Clinical studies have demonstrated the potential of MDSC-targeted strategies to improve treatment efficacy. However, challenges remain in achieving specificity and effectiveness in MDSC-targeted therapies, emphasizing the need for a deeper understanding of their biology. This review summarizes the origin, classification, and biological characteristics of MDSCs, their dual roles in tumor progression, and their clinical significance. We also discuss recent advances in clinical and preclinical studies, including both traditional targeted therapies and emerging innovative strategies. By integrating current findings, we aim to provide a comprehensive perspective on the role of MDSCs in cancer and valuable insights for advancing cancer treatment and drug development.

Keywords

myeloid-derived suppressor cells (MDSCs) / MDSC phenotype / tumor microenvironment (TME) / tumor-promoting mechanisms / biomarker potential / therapeutic strategy

Cite this article

Download citation ▾
Tianying Hu, Jianxue Zhai, Zhanda Yang, Jiajia Peng, Chuxuan Wang, Xinyao Liu, Yawen Li, Jiaqi Yao, Fengxi Chen, Haixia Li, Taixue An, Zongcai Liu, Haifang Wang. Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations. MedComm, 2025, 6(6): e70231 DOI:10.1002/mco2.70231

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

J. A. Bennett, V. S. Rao, and M. S. Mitchell, “Systemic bacillus Calmette-Guérin (BCG) activates natural suppressor cells,” PNAS 75, no. 10 (1978): 5142-5144.

[2]

E. J. Lappat and M. Cawein, “A Study of the Leukemoid Response to Transplantable A-280 Tumor in Mice,” Cancer Research 24 (1964): 302-311.

[3]

B. Almand, J. R. Resser, B. Lindman, et al., “Clinical significance of defective dendritic cell differentiation in cancer,” Clinical Cancer Research 6, no. 5 (2000): 1755-1766.

[4]

J. A. Bennett and M. S. Mitchell, “Induction of suppressor cells by intravenous administration of Bacillus Calmette-Guérin and its modulation by cyclophosphamide,” Biochemical Pharmacology 28, no. 12 (1979): 1947-1952.

[5]

A. K. Duwe and S. K. Singhal, “The immunoregulatory role of bone marrow. I. Suppression of the induction of antibody responses to T-dependent and T-independent antigens by cells in the bone marrow,” Cellular Immunology 43, no. 2 (1979): 362-371.

[6]

B. Almand, J. I. Clark, E. Nikitina, et al., “Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer,” Journal of Immunology 166, no. 1 (2001): 678-689.

[7]

D. M. Lathers, J. I. Clark, N. J. Achille, and M. R. Young, “Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3,” Cancer Immunology, Immunotherapy 53, no. 5 (2004): 422-430.

[8]

N. Mirza, M. Fishman, I. Fricke, et al., “All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients,” Cancer Research 66, no. 18 (2006): 9299-9307.

[9]

J. E. Talmadge and D. I. Gabrilovich, “History of myeloid-derived suppressor cells,” Nature Reviews Cancer 13, no. 10 (2013): 739-752.

[10]

S. Hegde, A. M. Leader, and M. Merad, “MDSC: Markers, development, states, and unaddressed complexity,” Immunity 54, no. 5 (2021): 875-884.

[11]

J. Lu, Y. Luo, D. Rao, et al., “Myeloid-derived suppressor cells in cancer: Therapeutic targets to overcome tumor immune evasion,” Exp Hematol Oncol 13, no. 1 (2024): 39.

[12]

D. I. Gabrilovich, V. Bronte, S. H. Chen, et al., “The terminology issue for myeloid-derived suppressor cells,” Cancer Research 67, no. 1 (2007): 425. author reply 426.

[13]

K. Li, H. Shi, B. Zhang, et al., “Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer,” Signal Transduct Target Ther 6, no. 1 (2021): 362.

[14]

N. Karin, “The Development and Homing of Myeloid-Derived Suppressor Cells: From a Two-Stage Model to a Multistep Narrative,” Frontiers in immunology 11 (2020): 557586.

[15]

J. Zhou, Y. Nefedova, A. Lei, and D. Gabrilovich, “Neutrophils and PMN-MDSC: Their biological role and interaction With stromal cells,” Seminars in Immunology 35 (2018): 19-28.

[16]

L. van Vlerken-Ysla, Y. Y. Tyurina, V. E. Kagan, and D. I. Gabrilovich, “Functional states of myeloid cells in cancer,” Cancer Cell 41, no. 3 (2023): 490-504.

[17]

P. De Cicco, G. Ercolano, and A. Ianaro, “The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion,” Frontiers in immunology 11 (2020): 1680.

[18]

C. Groth, X. Hu, R. Weber, et al., “Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) During tumour progression,” British Journal of Cancer 120, no. 1 (2019): 16-25.

[19]

S. He, L. Zheng, and C. Qi, “Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy,” Molecular cancer 24, no. 1 (2025): 5.

[20]

D. I. Gabrilovich and S. Nagaraj, “Myeloid-derived suppressor cells as regulators of the immune system,” Nature Reviews Immunology 9, no. 3 (2009): 162-174.

[21]

T. Zhang, Y. He, G. C. W. Man, Y. Ding, C. C. Wang, and J. P. W. Chung, “Myeloid-derived suppressor cells: A new emerging player in endometriosis,” Int Rev Cell Mol Biol 375 (2023): 191-220.

[22]

J. Cai, Y. Cui, J. Yang, and S. Wang, “Epithelial-mesenchymal transition: When tumor cells meet myeloid-derived suppressor cells,” Biochim Biophys Acta Rev Cancer 1876, no. 1 (2021): 188564.

[23]

J. N. Cheng, Y. X. Yuan, B. Zhu, and Q. Jia, “Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression,” Frontiers in Cell and Developmental Biology 9 (2021): 740827.

[24]

R. Salvia, L. G. Rico, T. Morán, et al., “Prognostic Significance of PD-L1 Expression on Circulating Myeloid-Derived Suppressor Cells in NSCLC Patients Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors,” International Journal of Molecular Sciences 25, no. 22 (2024).

[25]

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.

[26]

S. M. Park and J. I. Youn, “Role of myeloid-derived suppressor cells in immune checkpoint inhibitor therapy in cancer,” Arch Pharm Res 42, no. 7 (2019): 560-566.

[27]

K. Okla, I. Wertel, A. Wawruszak, M. Bobiński, and J. Kotarski, “Blood-based analyses of cancer: Circulating myeloid-derived suppressor cells—is a new era coming?,” Critical Reviews in Clinical Laboratory Sciences 55, no. 6 (2018): 376-407.

[28]

S. T. Barry, D. I. Gabrilovich, O. J. Sansom, A. D. Campbell, and J. P. Morton, “Therapeutic targeting of tumour myeloid cells,” Nature Reviews Cancer 23, no. 4 (2023): 216-237.

[29]

E. Nourbakhsh, A. Mohammadi, M. Salemizadeh Parizi, A. Mansouri, and F. Ebrahimzadeh, “Role of Myeloid-derived suppressor cell (MDSC) in autoimmunity and its potential as a therapeutic target,” Inflammopharmacology 29, no. 5 (2021): 1307-1315.

[30]

A. Grover, E. Sanseviero, E. Timosenko, and D. I. Gabrilovich, “Myeloid-Derived Suppressor Cells: A Propitious Road to Clinic,” Cancer discovery 11, no. 11 (2021): 2693-2706.

[31]

V. Bronte, S. Brandau, S. H. Chen, et al., “Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards,” Nature Communications 7 (2016): 12150.

[32]

Z. Hao, R. Li, Y. Wang, S. Li, Z. Hong, and Z. Han, “Landscape of Myeloid-derived Suppressor Cell in Tumor Immunotherapy,” Biomarker Research 9, no. 1 (2021): 77.

[33]

J. M. Haverkamp, A. M. Smith, R. Weinlich, et al., “Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways,” Immunity 41, no. 6 (2014): 947-959.

[34]

S. Zheng, W. Wang, L. Shen, Y. Yao, W. Xia, and C. Ni, “Tumor battlefield Within inflamed, excluded or desert immune phenotypes: The mechanisms and strategies,” Exp Hematol Oncol 13, no. 1 (2024): 80.

[35]

X. Cheng, H. Wang, Z. Wang, B. Zhu, and H. Long, “Tumor-associated myeloid cells in cancer immunotherapy,” Journal of hematology & oncology 16, no. 1 (2023): 71.

[36]

Y. Yin, W. Feng, J. Chen, et al., “Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: From bench to bedside,” Exp Hematol Oncol 13, no. 1 (2024): 72.

[37]

C. A. Corzo, T. Condamine, L. Lu, et al., “HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment,” Journal of Experimental Medicine 207, no. 11 (2010): 2439-2453.

[38]

V. Kumar, S. Patel, E. Tcyganov, and D. I. Gabrilovich, “The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment,” Trends in Immunology 37, no. 3 (2016): 208-220.

[39]

K. E. Cole, Q. P. Ly, M. A. Hollingsworth, et al., “Human splenic myeloid derived suppressor cells: Phenotypic and clustering analysis,” Cellular Immunology 363 (2021): 104317.

[40]

E. M. Mazza, A. Zoso, S. Mandruzzato, et al., “Gene expression profiling of human fibrocytic myeloid-derived suppressor cells (f-MDSCs),” Genom Data 2 (2014): 389-392.

[41]

Q. Li, P. Y. Pan, P. Gu, D. Xu, and S. H. Chen, “Role of immature myeloid Gr-1+ cells in the development of antitumor immunity,” Cancer Research 64, no. 3 (2004): 1130-1139.

[42]

D. I. Gabrilovich, S. Ostrand-Rosenberg, and V. Bronte, “Coordinated regulation of myeloid cells by tumours,” Nature Reviews Immunology 12, no. 4 (2012): 253-268.

[43]

F. Geissmann, M. G. Manz, S. Jung, M. H. Sieweke, M. Merad, and K. Ley, “Development of monocytes, macrophages, and dendritic cells,” Science 327, no. 5966 (2010): 656-661.

[44]

F. Veglia, M. Perego, and D. Gabrilovich, “Myeloid-derived suppressor cells coming of age,” Nature Immunology 19, no. 2 (2018): 108-119.

[45]

T. Condamine, J. Mastio, and D. I. Gabrilovich, “Transcriptional regulation of myeloid-derived suppressor cells,” J Leukoc Biol 98, no. 6 (2015): 913-922.

[46]

S. Ostrand-Rosenberg and P. Sinha, “Myeloid-derived suppressor cells: Linking inflammation and cancer,” Journal of Immunology 182, no. 8 (2009): 4499-4506.

[47]

P. C. Rodriguez, D. G. Quiceno, and A. C. Ochoa, “L-arginine availability regulates T-lymphocyte cell-cycle progression,” Blood 109, no. 4 (2007): 1568-1573.

[48]

S. Ostrand-Rosenberg, D. W. Beury, K. H. Parker, and L. A. Horn, “Survival of the fittest: How myeloid-derived suppressor cells survive in the inhospitable tumor microenvironment,” Cancer Immunology, Immunotherapy 69, no. 2 (2020): 215-221.

[49]

N. Du, H. Wan, H. Guo, X. Zhang, and X. Wu, “Myeloid-derived suppressor cells as important factors and potential targets for breast cancer progression,” Zhejiang Da Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences 53, no. 6 (2024): 785-795.

[50]

N. Horikawa, K. Abiko, N. Matsumura, et al., “Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment,” British Journal of Cancer 122, no. 6 (2020): 778-788.

[51]

X. Liu, R. Tang, J. Xu, et al., “CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma,” Gut 72, no. 12 (2023): 2329-2343.

[52]

G. B. B. Buzaglo, G. D. Telles, R. B. Araújo, et al., “The Therapeutic Potential of Physical Exercise in Cancer: The Role of Chemokines,” International Journal of Molecular Sciences 25, no. 24 (2024).

[53]

J. Che, R. Song, B. Chen, and X. Dong, “Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead,” European Journal of Medicinal Chemistry 185 (2020): 111853.

[54]

C. Wang, X. Zheng, J. Zhang, et al., “CD300ld on neutrophils is required for tumour-driven immune suppression,” Nature 621, no. 7980 (2023): 830-839.

[55]

J. L. Liu, X. Xu, Y. Rixiati, et al., “Dysfunctional circadian clock accelerates cancer metastasis by intestinal microbiota triggering accumulation of myeloid-derived suppressor cells,” Cell metabolism 36, no. 6 (2024): 1320-1334. e1329.

[56]

T. Condamine, V. Kumar, I. R. Ramachandran, et al., “ER stress regulates myeloid-derived suppressor cell fate Through TRAIL-R-mediated apoptosis,” Journal of Clinical Investigation 124, no. 6 (2014): 2626-2639.

[57]

K. Mirjačić Martinović, A. Vuletić, N. Tišma Miletić, et al., “Increased circulating monocyte MDSCs positively correlate With serum Interleukin-10 in metastatic melanoma patients,” Innate Immun 29, no. 3-4 (2023): 37-44.

[58]

K. M. Hart, K. T. Byrne, M. J. Molloy, E. M. Usherwood, and B. Berwin, “IL-10 immunomodulation of myeloid cells regulates a murine model of ovarian cancer,” Frontiers in immunology 2 (2011): 29.

[59]

D. W. Beury, K. H. Parker, M. Nyandjo, P. Sinha, and K. A. Carter, “Ostrand-Rosenberg S. Cross-talk Among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors,” J Leukoc Biol 96, no. 6 (2014): 1109-1118.

[60]

S. Ostrand-Rosenberg, P. Sinha, D. W. Beury, and V. K. Clements, “Cross-talk Between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression,” Seminars in Cancer Biology 22, no. 4 (2012): 275-281.

[61]

C. E. Hu, J. Gan, R. D. Zhang, Y. R. Cheng, and G. J. Huang, “Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function,” Scandinavian Journal of Gastroenterology 46, no. 2 (2011): 156-164.

[62]

H. Groux, “Type 1 T-regulatory cells: Their role in the control of immune responses,” Transplantation 75, no. 9 (2003): 8s-12s. Suppl.

[63]

K. M. Sullivan, X. Jiang, P. Guha, et al., “Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases,” Gut 72, no. 2 (2023): 325-337.

[64]

V. M. Ravi, N. Neidert, P. Will, et al., “T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10,” Nature Communications 13, no. 1 (2022): 925.

[65]

B. G. Nixon, S. Gao, X. Wang, and L.i MO, “TGFβ control of immune responses in cancer: A holistic immuno-oncology perspective,” Nature Reviews Immunology 23, no. 6 (2023): 346-362.

[66]

Z. Wang, Y. Hu, J. Song, P. Ma, and H. Xia, “Polymorphonuclear myeloid-derived suppressor cells regulates immune recovery During HIV infection Through PD-L1 and TGF-β pathways,” Frontiers in Cellular and Infection Microbiology 14 (2024): 1516421.

[67]

B. Niu, T. Tian, L. Wang, et al., “CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-β,” Acta Pharm Sin B 14, no. 8 (2024): 3711-3729.

[68]

L. Gorelik, S. Constant, and R. A. Flavell, “Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation,” Journal of Experimental Medicine 195, no. 11 (2002): 1499-1505.

[69]

L. Gorelik, P. E. Fields, and R. A. Flavell, “Cutting edge: TGF-beta inhibits Th type 2 development Through inhibition of GATA-3 expression,” Journal of Immunology 165, no. 9 (2000): 4773-4777.

[70]

K. Chikamatsu, K. Sakakura, M. Toyoda, K. Takahashi, T. Yamamoto, and K. Masuyama, “Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck,” Cancer Science 103, no. 6 (2012): 976-983.

[71]

A. J. Gunderson, T. Yamazaki, K. McCarty, et al., “TGFβ suppresses CD8(+) T cell expression of CXCR3 and tumor trafficking,” Nature Communications 11, no. 1 (2020): 1749.

[72]

L. Gneo, N. Rizkalla, R. Hejmadi, F. Mussai, C. de Santo, and G. Middleton, “TGF-β orchestrates the phenotype and function of monocytic myeloid-derived suppressor cells in colorectal cancer,” Cancer Immunology, Immunotherapy 71, no. 7 (2022): 1583-1596.

[73]

L. Li, R. Yu, T. Cai, et al., “Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment,” International Immunopharmacology 88 (2020): 106939.

[74]

T. Condamine and D. I. Gabrilovich, “Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function,” Trends in Immunology 32, no. 1 (2011): 19-25.

[75]

H. Li, Y. Han, Q. Guo, M. Zhang, and X. Cao, “Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells Through membrane-bound TGF-beta 1,” Journal of Immunology 182, no. 1 (2009): 240-249.

[76]

M. Lima-Rodrigues, A. Valle-Fernandes, N. Lamas, et al., “A new model of laryngitis: Neuropeptide, cyclooxygenase, and cytokine profile,” Laryngoscope 118, no. 1 (2008): 78-86.

[77]

N. Hashemi Goradel, M. Najafi, E. Salehi, B. Farhood, and K. Mortezaee, “Cyclooxygenase-2 in cancer: A review,” Journal of Cellular Physiology 234, no. 5 (2019): 5683-5699.

[78]

S. K. Juin, S. Ghosh, and S. Majumdar, “Glycyrrhizic acid facilitates anti-tumor immunity by attenuating Tregs and MDSCs: An immunotherapeutic approach,” International Immunopharmacology 88 (2020): 106932.

[79]

H. Lee, S. Jung, G. Gong, B. Lim, and H. J. Lee, “Association of cyclooxygenase-2 expression With endoplasmic reticulum stress and autophagy in triple-negative breast cancer,” PLoS ONE 18, no. 8 (2023): e0289627.

[80]

P. C. Rodriguez, C. P. Hernandez, D. Quiceno, et al., “Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma,” Journal of Experimental Medicine 202, no. 7 (2005): 931-939.

[81]

Y. Xu, W. Zhao, J. Xu, et al., “Activated hepatic stellate cells promote liver cancer by induction of myeloid-derived suppressor cells Through cyclooxygenase-2,” Oncotarget 7, no. 8 (2016): 8866-8878.

[82]

N. Obermajer, R. Muthuswamy, J. Lesnock, R. P. Edwards, and P. Kalinski, “Positive feedback Between PGE2 and COX2 redirects the differentiation of human dendritic cells Toward stable myeloid-derived suppressor cells,” Blood 118, no. 20 (2011): 5498-5505.

[83]

A. H. Zea, P. C. Rodriguez, M. B. Atkins, et al., “Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion,” Cancer Research 65, no. 8 (2005): 3044-3048.

[84]

P. C. Rodriguez, D. G. Quiceno, J. Zabaleta, et al., “Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses,” Cancer Research 64, no. 16 (2004): 5839-5849.

[85]

X. Ye, X. Huang, X. Fu, et al., “Myeloid-Like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis,” Journal of hematology & oncology 16, no. 1 (2023): 46.

[86]

V. Bronte, P. Serafini, C. De Santo, et al., “IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice,” Journal of Immunology 170, no. 1 (2003): 270-278.

[87]

P. C. Rodriguez, M. S. Ernstoff, C. Hernandez, et al., “Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes,” Cancer Research 69, no. 4 (2009): 1553-1560.

[88]

P. C. Rodriguez, A. H. Zea, K. S. Culotta, J. Zabaleta, J. B. Ochoa, and A. C. Ochoa, “Regulation of T cell receptor CD3zeta chain expression by L-arginine,” Journal of Biological Chemistry 277, no. 24 (2002): 21123-21129.

[89]

A. H. Zea, P. C. Rodriguez, K. S. Culotta, et al., “L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes,” Cellular Immunology 232, no. 1-2 (2004): 21-31.

[90]

A. Sica and V. Bronte, “Altered macrophage differentiation and immune dysfunction in tumor development,” Journal of Clinical Investigation 117, no. 5 (2007): 1155-1166.

[91]

Y. Liu, C. C. Wong, Y. Ding, et al., “Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice,” Nature microbiology 9, no. 6 (2024): 1467-1482.

[92]

A. M. K. Law, F. Valdes-Mora, and D. Gallego-Ortega, “Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer,” Cells 9, no. 3 (2020).

[93]

B. Molon, S. Ugel, F. Del Pozzo, et al., “Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells,” Journal of Experimental Medicine 208, no. 10 (2011): 1949-1962.

[94]

C. A. Corzo, M. J. Cotter, P. Cheng, et al., “Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells,” Journal of Immunology 182, no. 9 (2009): 5693-5701.

[95]

J. Huang, Y. Zhao, K. Zhao, K. Yin, and S. Wang, “Function of reactive oxygen species in myeloid-derived suppressor cells,” Frontiers in immunology 14 (2023): 1226443.

[96]

S. Kusmartsev and D. I. Gabrilovich, “Inhibition of myeloid cell differentiation in cancer: The role of reactive oxygen species,” J Leukoc Biol 74, no. 2 (2003): 186-196.

[97]

J. Yu, W. Du, F. Yan, et al., “Myeloid-derived suppressor cells suppress antitumor immune responses Through IDO expression and correlate With lymph node metastasis in patients With breast cancer,” Journal of Immunology 190, no. 7 (2013): 3783-3797.

[98]

F. Li, R. Zhang, S. Li, and J. Liu, “IDO1: An important immunotherapy target in cancer treatment,” International Immunopharmacology 47 (2017): 70-77.

[99]

J. D. Mezrich, J. H. Fechner, X. Zhang, B. P. Johnson, W. J. Burlingham, and C. A. Bradfield, “An interaction Between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells,” Journal of Immunology 185, no. 6 (2010): 3190-3198.

[100]

R. B. Holmgaard, D. Zamarin, A. Lesokhin, T. Merghoub, and J. D. Wolchok, “Targeting myeloid-derived suppressor cells With colony stimulating factor-1 receptor blockade can reverse immune resistance to immunotherapy in indoleamine 2,3-dioxygenase-expressing tumors,” EBioMedicine 6 (2016): 50-58.

[101]

G. C. Prendergast, W. J. Malachowski, A. Mondal, P. Scherle, and A. J. Muller, “Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer,” Int Rev Cell Mol Biol 336 (2018): 175-203.

[102]

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.

[103]

J. P. Antonios, H. Soto, R. G. Everson, et al., “Immunosuppressive tumor-infiltrating myeloid cells mediate adaptive immune resistance via a PD-1/PD-L1 mechanism in glioblastoma,” Neuro-oncol 19, no. 6 (2017): 796-807.

[104]

M. Z. Noman, G. Desantis, B. Janji, et al., “PD-L1 is a novel direct target of HIF-1α, and its blockade Under hypoxia enhanced MDSC-mediated T cell activation,” Journal of Experimental Medicine 211, no. 5 (2014): 781-790.

[105]

G. L. Semenza, “Intratumoral Hypoxia and Mechanisms of Immune Evasion Mediated by Hypoxia-Inducible Factors,” Physiology (Bethesda, Md.) 36, no. 2 (2021): 73-83.

[106]

G. Qin, S. Liu, J. Liu, et al., “Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells,” Signal Transduct Target Ther 8, no. 1 (2023): 164.

[107]

T. J. Moon, H. M. Ta, A. Bhalotia, et al., “Nanoparticles targeting immune checkpoint protein VISTA induce potent antitumor immunity,” Journal for ImmunoTherapy of Cancer 12, no. 8 (2024).

[108]

D. Roy, C. Gilmour, S. Patnaik, and L. L. Wang, “Combinatorial blockade for cancer immunotherapy: Targeting emerging immune checkpoint receptors,” Frontiers in immunology 14 (2023): 1264327.

[109]

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).

[110]

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.

[111]

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.

[112]

R. Ren, X. Chang, C. Chen, H. Yu, and L. Han, “VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature,” Open Med (Wars) 18, no. 1 (2023): 20230866.

[113]

L. Wang, B. Jia, D. F. Claxton, et al., “VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients With AML,” Oncoimmunology 7, no. 9 (2018): e1469594.

[114]

J. Deng, J. Li, A. Sarde, et al., “Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment,” Cancer immunology research 7, no. 7 (2019): 1079-1090.

[115]

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.

[116]

Z. Chen, R. Yuan, S. Hu, W. Yuan, and Z. Sun, “Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression,” Frontiers in immunology 13 (2022): 817942.

[117]

R. Kalluri and V. S. LeBleu, “The biology, function, and biomedical applications of exosomes,” Science 367, no. 6478 (2020).

[118]

J. Liu, L. Ren, S. Li, et al., “The biology, function, and applications of exosomes in cancer,” Acta Pharm Sin B 11, no. 9 (2021): 2783-2797.

[119]

M. Lu, W. Shao, H. Xing, and Y. Huang, “Extracellular vesicle-based nucleic acid delivery,” Interdisciplinary MEDICINE 1, no. 2 (2023): e20220007.

[120]

Q. H. Xie, J. Q. Zheng, J. Y. Ding, et al., “Exosome-Mediated Immunosuppression in Tumor Microenvironments,” Cells 11, no. 12 (2022).

[121]

X. Liu, Q. Wei, Z. Sun, et al., “Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management,” Interdisciplinary MEDICINE 1, no. 4 (2023): e20230019.

[122]

L. Geis-Asteggiante, A. T. Belew, V. K. Clements, et al., “Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions,” Journal of Proteome Research 17, no. 1 (2018): 486-498.

[123]

L. Li, J. Zhang, W. Diao, et al., “MicroRNA-155 and MicroRNA-21 promote the expansion of functional myeloid-derived suppressor cells,” Journal of Immunology 192, no. 3 (2014): 1034-1043.

[124]

M. H. Rashid, T. F. Borin, R. Ara, et al., “Critical immunosuppressive effect of MDSC‑derived exosomes in the tumor microenvironment,” Oncology Reports 45, no. 3 (2021): 1171-1181.

[125]

J. Liu, J. Liu, G. Qin, et al., “MDSCs-derived GPR84 induces CD8(+) T-cell senescence via p53 activation to suppress the antitumor response,” Journal for ImmunoTherapy of Cancer 11, no. 11 (2023).

[126]

S. Brabletz, H. Schuhwerk, T. Brabletz, and M. P. Stemmler, “Dynamic EMT: A multi-tool for tumor progression,” Embo Journal 40, no. 18 (2021): e108647.

[127]

Z. Liu, J. Wang, S. Li, et al., “Prognostic prediction and immune infiltration analysis based on ferroptosis and EMT state in hepatocellular carcinoma,” Frontiers in immunology 13 (2022): 1076045.

[128]

A. Glaviano, H. S. Lau, L. M. Carter, et al., “Harnessing the tumor microenvironment: Targeted cancer therapies Through modulation of epithelial-mesenchymal transition,” Journal of hematology & oncology 18, no. 1 (2025): 6.

[129]

F. Veglia, E. Sanseviero, and D. I. Gabrilovich, “Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity,” Nature Reviews Immunology 21, no. 8 (2021): 485-498.

[130]

X. Ma, M. Wang, T. Yin, Y. Zhao, and X. Wei, “Myeloid-Derived Suppressor Cells Promote Metastasis in Breast Cancer After the Stress of Operative Removal of the Primary Cancer,” Frontiers in oncology 9 (2019): 855.

[131]

A. Luo, M. Meng, G. Wang, et al., “Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling,” J Breast Cancer 23, no. 2 (2020): 141-161.

[132]

E. K. Vetsika, A. Koukos, and A. Kotsakis, “Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer,” Cells 8, no. 12 (2019).

[133]

L. Yang, L. M. DeBusk, K. Fukuda, et al., “Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis,” Cancer Cell 6, no. 4 (2004): 409-421.

[134]

M. Benguigui, A. Vorontsova, M. Timaner, et al., “Bv8 Blockade Sensitizes Anti-PD1 Therapy Resistant Tumors,” Frontiers in immunology 13 (2022): 903591.

[135]

X. Qu, G. Zhuang, L. Yu, G. Meng, and N. Ferrara, “Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells: Key role of Stat3 signaling,” Journal of Biological Chemistry 287, no. 23 (2012): 19574-19584.

[136]

Y. Liu and X. Cao, “Characteristics and Significance of the Pre-metastatic Niche,” Cancer Cell 30, no. 5 (2016): 668-681.

[137]

D. I. Gabrilovich, “Myeloid-Derived Suppressor Cells,” Cancer immunology research 5, no. 1 (2017): 3-8.

[138]

D. Zeng, M. Wang, J. Wu, et al., “Immunosuppressive Microenvironment Revealed by Immune Cell Landscape in Pre-metastatic Liver of Colorectal Cancer,” Frontiers in oncology 11 (2021): 620688.

[139]

D. Wang, H. Sun, J. Wei, B. Cen, and R. N. DuBois, “CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer,” Cancer Research 77, no. 13 (2017): 3655-3665.

[140]

Y. Zheng, N. Wang, S. Wang, J. Zhang, B. Yang, and Z. Wang, “Chronic psychological stress promotes breast cancer pre-metastatic niche formation by mobilizing splenic MDSCs via TAM/CXCL1 signaling,” Journal of Experimental & Clinical Cancer Research 42, no. 1 (2023): 129.

[141]

G. Karpathiou, F. Orlando, J. M. Dumollard, M. Mobarki, C. Chauleur, and M. Péoc'h, “The Premetastatic Lymph Node Niche in Gynecologic Cancer,” International Journal of Molecular Sciences 24, no. 4 (2023).

[142]

N. T. Nguyen, A. Mitsuhashi, H. Ogino, et al., “S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor,” Cancer Science 114, no. 2 (2023): 384-398.

[143]

X. Zeng, G. Liao, S. Li, et al., “Eliminating METTL1-mediated accumulation of PMN-MDSCs prevents hepatocellular carcinoma recurrence After radiofrequency ablation,” Hepatology 77, no. 4 (2023): 1122-1138.

[144]

Y. Wu, M. Yi, M. Niu, Q. Mei, and K. Wu, “Myeloid-derived suppressor cells: An emerging target for anticancer immunotherapy,” Molecular cancer 21, no. 1 (2022): 184.

[145]

T. Liang, T. Tao, K. Wu, et al., “Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer,” Adv Sci (Weinh) 10, no. 31 (2023): e2303230.

[146]

T. Kobayashi, M. Nagata, T. Hachiya, et al., “Increased circulating polymorphonuclear myeloid-derived suppressor cells are associated With prognosis of metastatic castration-resistant prostate cancer,” Frontiers in immunology 15 (2024): 1372771.

[147]

C. Meyer, L. Cagnon, C. M. Costa-Nunes, et al., “Frequencies of circulating MDSC correlate With clinical outcome of melanoma patients treated With ipilimumab,” Cancer Immunology, Immunotherapy 63, no. 3 (2014): 247-257.

[148]

Y. P. de Coaña, M. Wolodarski, I. Poschke, et al., “Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors With advanced melanoma,” Oncotarget 8, no. 13 (2017): 21539-21553.

[149]

H. H. Ni, L. Zhang, H. Huang, S. Q. Dai, and J. Li, “Connecting METTL3 and intratumoural CD33(+) MDSCs in predicting clinical outcome in cervical cancer,” Journal of translational medicine 18, no. 1 (2020): 393.

[150]

C. Bergenfelz, A. Roxå, M. Mehmeti, K. Leandersson, and A. M. Larsson, “Clinical relevance of systemic monocytic-MDSCs in patients With metastatic breast cancer,” Cancer Immunology, Immunotherapy 69, no. 3 (2020): 435-448.

[151]

T. Akiyama, T. Yasuda, T. Uchihara, et al., “Stromal Reprogramming Through Dual PDGFRα/β Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors,” Cancer Research 83, no. 5 (2023): 753-770.

[152]

T. Wu, X. Zhang, X. Liu, et al., “Single-cell sequencing reveals the immune microenvironment landscape related to anti-PD-1 resistance in metastatic colorectal cancer With high microsatellite instability,” BMC Medicine [Electronic Resource] 21, no. 1 (2023): 161.

[153]

H. R. Kim, S. M. Park, S. U. Seo, et al., “The Ratio of Peripheral Regulatory T Cells to Lox-1(+) Polymorphonuclear Myeloid-derived Suppressor Cells Predicts the Early Response to Anti-PD-1 Therapy in Patients With Non-Small Cell Lung Cancer,” American Journal of Respiratory and Critical Care Medicine 199, no. 2 (2019): 243-246.

[154]

J. I. Youn, S. M. Park, S. Park, et al., “Peripheral natural killer cells and myeloid-derived suppressor cells correlate With anti-PD-1 responses in non-small cell lung cancer,” Scientific Reports 10, no. 1 (2020): 9050.

[155]

J. Koh, Y. Kim, K. Y. Lee, et al., “MDSC subtypes and CD39 expression on CD8(+) T cells predict the efficacy of anti-PD-1 immunotherapy in patients With advanced NSCLC,” European Journal of Immunology 50, no. 11 (2020): 1810-1819.

[156]

M. Napolitano, C. D'Alterio, E. Cardone, et al., “Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients,” Oncotarget 6, no. 10 (2015): 8261-8270.

[157]

C. Jiménez-Cortegana, C. Galassi, V. Klapp, D. I. Gabrilovich, and L. Galluzzi, “Myeloid-Derived Suppressor Cells and Radiotherapy,” Cancer immunology research 10, no. 5 (2022): 545-557.

[158]

F. Koinis, E. K. Vetsika, D. Aggouraki, et al., “Effect of First-Line Treatment on Myeloid-Derived Suppressor Cells' Subpopulations in the Peripheral Blood of Patients With Non-Small Cell Lung Cancer,” Journal of thoracic oncology 11, no. 8 (2016): 1263-1272.

[159]

J. Wu, X. Zhao, Q. Sun, et al., “Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model,” Biomedicine & Pharmacotherapy 125 (2020): 109746.

[160]

L. He, X. Cheng, Y. Gu, et al., “Fruquintinib Combined With PD-1 Inhibitors for the Treatment of the Patients With Microsatellite Stability Metastatic Colorectal Cancer: Real-World Data,” Clinical Oncology (Royal College of Radiologists (Great Britain)) 38 (2024): 103700.

[161]

H. D. Kim, M. H. Ryu, S. Yoon, et al., “Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated With ramucirumab plus paclitaxel,” Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 32, no. 5 (2020): 621-630.

[162]

X. Zhao, R. Zhao, J. Wen, et al., “Anlotinib reduces the suppressive capacity of monocytic myeloid-derived suppressor cells and potentiates the immune microenvironment normalization window in a mouse lung cancer model,” Anti-Cancer Drugs 34, no. 9 (2023): 1018-1024.

[163]

R. Fan, H. Satilmis, N. Vandewalle, et al., “Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma,” Journal for ImmunoTherapy of Cancer 11, no. 1 (2023).

[164]

P. Xu, K. Yin, X. Tang, et al., “Metformin inhibits the function of granulocytic myeloid-derived suppressor cells in tumor-bearing mice,” Biomedicine & Pharmacotherapy 120 (2019): 109458.

[165]

C. Conche, F. Finkelmeier, M. Pešić, et al., “Combining ferroptosis induction With MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade,” Gut 72, no. 9 (2023): 1774-1782.

[166]

S. C. Robinson, K. A. Scott, J. L. Wilson, R. G. Thompson, A. E. Proudfoot, and F. R. Balkwill, “A chemokine receptor antagonist inhibits experimental breast tumor growth,” Cancer Research 63, no. 23 (2003): 8360-8365.

[167]

G. M. Haag, C. Springfeld, B. Grün, et al., “Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer—The PICCASSO phase I trial,” European Journal of Cancer 167 (2022): 112-122.

[168]

C. Iclozan, S. Antonia, A. Chiappori, D. T. Chen, and D. Gabrilovich, “Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients With extensive stage small cell lung cancer,” Cancer Immunology, Immunotherapy 62, no. 5 (2013): 909-918.

[169]

E. Stockfleth, G. F. L. Hofbauer, U. Reinhold, et al., “Topical resiquimod dosing regimens in patients With multiple actinic keratoses: A multicentre, partly placebo-controlled, double-blind clinical trial,” British Journal of Dermatology 180, no. 2 (2019): 297-305.

[170]

D. J. Jonker, L. Nott, T. Yoshino, et al., “Napabucasin versus placebo in refractory advanced colorectal cancer: A randomised phase 3 trial,” Lancet Gastroenterol Hepatol 3, no. 4 (2018): 263-270.

[171]

M. J. Reilley, P. McCoon, C. Cook, et al., “STAT3 antisense oligonucleotide AZD9150 in a subset of patients With heavily pretreated lymphoma: Results of a phase 1b trial,” Journal for ImmunoTherapy of Cancer 6, no. 1 (2018): 119.

[172]

Y. Oki, K. R. Kelly, I. Flinn, et al., “CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients With MYC-alterations: Results From an expanded phase I trial,” Haematologica 102, no. 11 (2017): 1923-1930.

[173]

A. J. Wagner, V. Ravi, R. F. Riedel, et al., “nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors,” Journal of Clinical Oncology 39, no. 33 (2021): 3660-3670.

[174]

F. Hossain, A. A. Al-Khami, D. Wyczechowska, et al., “Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies,” Cancer immunology research 3, no. 11 (2015): 1236-1247.

[175]

J. Le Naour, L. Galluzzi, L. Zitvogel, G. Kroemer, and E. Vacchelli, “Trial watch: IDO inhibitors in cancer therapy,” Oncoimmunology 9, no. 1 (2020): 1777625.

[176]

J. E. Walsh, A. M. Clark, T. A. Day, M. B. Gillespie, and M. R. Young, “Use of alpha,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration Into head and neck squamous cell carcinoma,” Human Immunology 71, no. 7 (2010): 659-665.

[177]

J. C. Hassel, H. Jiang, C. Bender, et al., “Tadalafil has biologic activity in human melanoma. Results of a pilot trial With Tadalafil in patients With metastatic Melanoma (TaMe),” Oncoimmunology 6, no. 9 (2017): e1326440.

[178]

J. D. Veltman, M. E. Lambers, M. van Nimwegen, et al., “COX-2 inhibition improves immunotherapy and is associated With decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function,” BMC cancer 10 (2010): 464.

[179]

J. A. Meyerhardt, Q. Shi, C. S. Fuchs, et al., “Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial,” Jama 325, no. 13 (2021): 1277-1286.

[180]

J. Garcia, H. I. Hurwitz, A. B. Sandler, et al., “Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook,” Cancer Treatment Reviews 86 (2020): 102017.

[181]

Y. Jiang, S. Qiao, L. Li, and X. Zhu, “Combination of radiotherapy and Anlotinib enhances benefit From immunotherapy to liver metastasis and abscopal tumor From lung cancer,” International Immunopharmacology 128 (2024): 111441.

[182]

G. Qin, J. Lian, L. Huang, et al., “Metformin blocks myeloid-derived suppressor cell accumulation Through AMPK-DACH1-CXCL1 axis,” Oncoimmunology 7, no. 7 (2018): e1442167.

[183]

H. Katoh, D. Wang, T. Daikoku, H. Sun, S. K. Dey, and R. N. Dubois, “CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis,” Cancer Cell 24, no. 5 (2013): 631-644.

[184]

S. L. Highfill, Y. Cui, A. J. Giles, et al., “Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy,” Science Translational Medicine 6, no. 237 (2014): 237ra267.

[185]

C. Blattner, V. Fleming, R. Weber, et al., “CCR5(+) Myeloid-Derived Suppressor Cells Are Enriched and Activated in Melanoma Lesions,” Cancer Research 78, no. 1 (2018): 157-167.

[186]

Y. Nefedova, M. Fishman, S. Sherman, X. Wang, A. A. Beg, and D. I. Gabrilovich, “Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells,” Cancer Research 67, no. 22 (2007): 11021-11028.

[187]

M. Lee, C. S. Park, Y. R. Lee, S. A. Im, S. Song, and C. K. Lee, “Resiquimod, a TLR7/8 agonist, promotes differentiation of myeloid-derived suppressor cells Into macrophages and dendritic cells,” Arch Pharm Res 37, no. 9 (2014): 1234-1240.

[188]

S. Zou, Q. Tong, B. Liu, W. Huang, Y. Tian, and X. Fu, “Targeting STAT3 in Cancer Immunotherapy,” Molecular cancer 19, no. 1 (2020): 145.

[189]

P. Guha, J. Gardell, J. Darpolor, et al., “STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells,” Oncogene 38, no. 4 (2019): 533-548.

[190]

R. Bitsch, A. Kurzay, F. Özbay Kurt, et al., “STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice,” Journal for ImmunoTherapy of Cancer 10, no. 3 (2022).

[191]

H. F. Wang, F. Ning, Z. C. Liu, et al., “Histone deacetylase inhibitors deplete myeloid-derived suppressor cells induced by 4T1 mammary tumors in vivo and in vitro,” Cancer Immunology, Immunotherapy 66, no. 3 (2017): 355-366.

[192]

D. Alizadeh, M. Trad, N. T. Hanke, et al., “Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer,” Cancer Research 74, no. 1 (2014): 104-118.

[193]

J. Vincent, G. Mignot, F. Chalmin, et al., “5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity,” Cancer Research 70, no. 8 (2010): 3052-3061.

[194]

T. Michels, G. V. Shurin, H. Naiditch, A. Sevko, V. Umansky, and M. R. Shurin, “Paclitaxel promotes differentiation of myeloid-derived suppressor cells Into dendritic cells in vitro in a TLR4-independent manner,” J Immunotoxicol 9, no. 3 (2012): 292-300.

[195]

J. A. Sparano, M. Wang, S. Martino, et al., “Weekly paclitaxel in the adjuvant treatment of breast cancer,” New England Journal of Medicine 358, no. 16 (2008): 1663-1671.

[196]

J. Zhou, S. S. Donatelli, D. L. Gilvary, et al., “Therapeutic targeting of myeloid-derived suppressor cells involves a novel mechanism mediated by clusterin,” Scientific Reports 6 (2016): 29521.

[197]

K. Li, J. Wang, Y. Xie, et al., “Reactive oxygen species/glutathione dual sensitive nanoparticles With encapsulation of miR155 and curcumin for synergized cancer immunotherapy,” J Nanobiotechnology 22, no. 1 (2024): 400.

[198]

H. F. Kramer, C. A. Witczak, E. B. Taylor, N. Fujii, M. F. Hirshman, and L. J. Goodyear, “AS160 regulates insulin- and contraction-stimulated glucose uptake in mouse skeletal muscle,” Journal of Biological Chemistry 281, no. 42 (2006): 31478-31485.

[199]

T. Wu, Y. Zhao, H. Wang, et al., “mTOR masters monocytic myeloid-derived suppressor cells in mice With allografts or tumors,” Scientific Reports 6 (2016): 20250.

[200]

K. Yu, Y. Wang, C. Yu, et al., “Regulatory effect of rapamycin on recruitment and function of myeloid-derived suppressor cells in heart failure,” International Immunopharmacology 141 (2024): 112965.

[201]

S. Dong, S. Liang, Z. Cheng, et al., “ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer,” Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022): 15.

[202]

R. B. Holmgaard, D. Zamarin, Y. Li, et al., “Tumor-Expressed IDO Recruits and Activates MDSCs in a Treg-Dependent Manner,” Cell reports 13, no. 2 (2015): 412-424.

[203]

J. C. Fleet, G. N. Burcham, R. D. Calvert, B. D. Elzey, and T. L. Ratliff, “1α, 25 Dihydroxyvitamin D (1,25(OH)(2)D) inhibits the T cell suppressive function of myeloid derived suppressor cells (MDSC),” Journal of Steroid Biochemistry and Molecular Biology 198 (2020): 105557.

[204]

P. Serafini, K. Meckel, M. Kelso, et al., “Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function,” Journal of Experimental Medicine 203, no. 12 (2006): 2691-2702.

[205]

Y. Mao, D. Sarhan, A. Steven, B. Seliger, R. Kiessling, and A. Lundqvist, “Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid-derived suppressor cells and recovers natural killer cell activity,” Clinical Cancer Research 20, no. 15 (2014): 4096-4106.

[206]

Y. Long, Z. Lu, S. Xu, et al., “Self-Delivery Micellar Nanoparticles Prevent Premetastatic Niche Formation by Interfering With the Early Recruitment and Vascular Destruction of Granulocytic Myeloid-Derived Suppressor Cells,” Nano Letters 20, no. 4 (2020): 2219-2229.

[207]

D. Kumar, V. C. Da Silva, and N. L. Chaves, “Myeloid‑derived suppressor cells as targets of emerging therapies and nanotherapies (Review),” Med Int (Lond) 4, no. 5 (2024): 46.

[208]

W. Zhu, X. Cheng, P. Xu, et al., “Radiotherapy-Driven Nanoprobes Targeting for Visualizing Tumor Infiltration Dynamics and Inducing Ferroptosis in Myeloid-Derived Suppressor Cells,” Journal of the American Chemical Society 146, no. 32 (2024): 22455-22468.

[209]

Z. Yang, H. Zuo, Y. Hou, et al., “Dual Oxygen-Supply Immunosuppression-Inhibiting Nanomedicine to Avoid the Intratumoral Recruitment of Myeloid-Derived Suppressor Cells,” Small (2024): e2406860.

[210]

L. R. Johnson, D. Y. Lee, J. S. Eacret, D. Ye, C. H. June, and A. J. Minn, “The immunostimulatory RNA RN7SL1 enables CAR-T cells to enhance autonomous and endogenous immune function,” Cell 184, no. 19 (2021): 4981-4995. e4914.

[211]

N. M. F. Abdalsalam, A. Ibrahim, M. A. Saliu, T. M. Liu, X. Wan, and D. Yan, “MDSC: A new potential breakthrough in CAR-T therapy for solid tumors,” Cell Communication and Signaling 22, no. 1 (2024): 612.

[212]

O. Adewunmi, Y. Shen, X. H. Zhang, and J. M. Rosen, “Targeted Inhibition of lncRNA Malat1 Alters the Tumor Immune Microenvironment in Preclinical Syngeneic Mouse Models of Triple-Negative Breast Cancer,” Cancer immunology research 11, no. 11 (2023): 1462-1479.

[213]

Y. Zhang, Y. Lei, Q. Ou, et al., “Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway,” BMC Biology 22, no. 1 (2024): 88.

[214]

T. T. Kwong, Z. Xiong, Y. Zhang, et al., “Overcoming Immunotherapy Resistance in Hepatocellular Carcinoma by Targeting Myeloid IL-8/CXCR2 Signaling,” Molecular Therapy (2025).

[215]

L. Pavelková, E. Táborská, L. A. Syding, et al., “Tissue contexture determines the pattern and density of tumor-infiltrating immune cells in HPV-associated squamous cell carcinomas of oropharynx and uterine cervix,” Transl Oncol 41 (2024): 101884.

[216]

A. Kiviaho, S. K. Eerola, H. M. L. Kallio, et al., “Single cell and spatial transcriptomics highlight the interaction of club-Like cells With immunosuppressive myeloid cells in prostate cancer,” Nature Communications 15, no. 1 (2024): 9949.

[217]

C. Jackson, C. Cherry, S. Bom, et al., “Distinct myeloid-derived suppressor cell populations in human glioblastoma,” Science 387, no. 6731 (2025): eabm5214.

[218]

C. Ma, Y. Li, M. Li, C. Lv, and Y. Tian, “Targeting immune checkpoints on myeloid cells: Current status and future directions,” Cancer Immunology, Immunotherapy 74, no. 2 (2025): 40.

RIGHTS & PERMISSIONS

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

AI Summary AI Mindmap
PDF

66

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/