Role of Neutrophils in Homeostasis and Diseases

Xingyu Chang , Yulin Liu , Junjun Qiu , Keqin Hua

MedComm ›› 2025, Vol. 6 ›› Issue (10) : e70390

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MedComm ›› 2025, Vol. 6 ›› Issue (10) : e70390 DOI: 10.1002/mco2.70390
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Role of Neutrophils in Homeostasis and Diseases

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Abstract

Neutrophils, constituting a predominant subset of innate immune cells in mammalian systems, play pivotal roles in pathogenic clearance and homeostatic maintenance. In the progressive development of cancer, neutrophils exert dual roles in both anticancer and procancer processes through their heterogeneity. In recent years, research into the role of neutrophils in cancer and various nontumor diseases has been continuously deepening. However, current research in this area remains incomplete. This review comprehensively summarizes the tissue homing dynamics, lifespan regulation, and physiological functions of neutrophils, starting from their development and heterogeneity. Furthermore, we delineate the dual regulatory functions of neutrophils in carcinogenesis, encompassing both tumor-suppressive mechanisms and protumor mechanisms. This section further synthesizes recent advancements in neutrophil-targeted therapeutic platforms and biomimetic delivery systems, while critically evaluating persistent methodological and translational challenges in clinical applications. In addition, we systematically analyze the role of neutrophils in non-neoplastic diseases and list several typical diseases, including infectious diseases. Finally, we also discuss current controversies and research perspectives on neutrophils. It is hoped that this review will deepen insights into the role of neutrophils in homeostasis and disease, while exploring their potential in disease treatment.

Keywords

cancer / homeostasis / immunotherapy / NETs / neutrophils

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Xingyu Chang, Yulin Liu, Junjun Qiu, Keqin Hua. Role of Neutrophils in Homeostasis and Diseases. MedComm, 2025, 6(10): e70390 DOI:10.1002/mco2.70390

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References

[1]

Hedrick and I. Malanchi, “Neutrophils in Cancer: Heterogeneous and Multifaceted,” Nature Reviews Immunology 22, no. 3 (2022): 173-187.

[2]

K. Kienle and T. Lämmermann, “Neutrophil Swarming: An Essential Process of the Neutrophil Tissue Response,” Immunological Reviews 273, no. 1 (2016): 76-93.

[3]

R. Herro and H. L Grimes, “The Diverse Roles of Neutrophils From Protection to Pathogenesis,” Nature Immunology 25, no. 12 (2024): 2209-2219.

[4]

M. S. F. Ng, I. Kwok, L. Tan, et al., “Deterministic Reprogramming of Neutrophils Within Tumors,” Science (New York, NY) 383, no. 6679 (2024): eadf6493.

[5]

S. Chen, Q. Zhang, L. Lu, et al., “Heterogeneity of Neutrophils in Cancer: One Size Does Not Fit All,” Cancer Biol Med 19, no. 12 (2022): 1629-1648.

[6]

D. Maier-Begandt, N. Alonso-Gonzalez, and L. Klotz, “Neutrophils-biology and Diversity,” Nephrology, Dialysis, Transplantation 39, no. 10 (2024): 1551-1564.

[7]

F. Zhang, Y. Xia, J. Su, et al., “Neutrophil Diversity and Function in Health and Disease,” Signal Transduct Target Ther 9, no. 1 (2024): 343.

[8]

N. Borregaard, “Neutrophils, From Marrow to Microbes,” Immunity 33, no. 5 (2010): 657-670.

[9]

I. Di Ceglie, S. Carnevale, A. Rigatelli, et al., “Immune Cell Networking in Solid Tumors: Focus on Macrophages and Neutrophils,” Frontiers in immunology 15 (2024): 1341390.

[10]

M. Palomino-Segura, J. Sicilia, I. Ballesteros, et al., “Strategies of Neutrophil Diversification,” Nature Immunology 24, no. 4 (2023): 575-584.

[11]

E. Ramon-Gil, D. Geh, and J. Leslie, “Harnessing Neutrophil Plasticity for HCC Immunotherapy,” Essays in Biochemistry 67, no. 6 (2023): 941-955.

[12]

W. He, L. Yan, D. Hu, et al., “Neutrophil Heterogeneity and Plasticity: Unveiling the Multifaceted Roles in Health and Disease,” MedComm 6, no. 2 (2025): e70063.

[13]

X. Xie, Q. Shi, P. Wu, et al., “Single-cell Transcriptome Profiling Reveals Neutrophil Heterogeneity in Homeostasis and Infection,” Nature Immunology 21, no. 9 (2020): 1119-1133.

[14]

J. Pillay, V. M. Kamp, E. van Hoffen, et al., “A Subset of Neutrophils in human Systemic Inflammation Inhibits T Cell Responses Through Mac-1,” The Journal of Clinical Investigation 122, no. 1 (2012): 327-336.

[15]

L. G. Ng, R. Ostuni, and A. Hidalgo, “Heterogeneity of Neutrophils,” Nature Reviews Immunology 19, no. 4 (2019): 255-265.

[16]

J. M. Adrover, J. A. Nicolás-Ávila, and A. Hidalgo, “Aging: A Temporal Dimension for Neutrophils,” Trends in Immunology 37, no. 5 (2016): 334-345.

[17]

K. Man, A. Loudon, and A. Chawla, “Immunity Around the Clock,” Science (New York, NY) 354, no. 6315 (2016): 999-1003.

[18]

M. D'Ambrosio and J. Gil, “Reshaping of the Tumor Microenvironment by Cellular Senescence: An Opportunity for Senotherapies,” Developmental Cell 58, no. 12 (2023): 1007-1021.

[19]

Z. Dong, Y. Luo, Z. Yuan, et al., “Cellular Senescence and SASP in Tumor Progression and Therapeutic Opportunities,” Molecular Cancer 23, no. 1 (2024): 181.

[20]

J.-P. Coppé, P.-Y. Desprez, A. Krtolica, et al., “The Senescence-associated Secretory Phenotype: The Dark Side of Tumor Suppression,” Annual Review of Pathology 5 (2010): 99-118.

[21]

J.-P. Coppé, C. K. Patil, F. Rodier, et al., “Senescence-associated Secretory Phenotypes Reveal Cell-nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor,” Plos Biology 6, no. 12 (2008): 2853-2868.

[22]

B. Wang, J. Han, J. H. Elisseeff, et al., “The Senescence-associated Secretory Phenotype and Its Physiological and Pathological Implications,” Nature Reviews Molecular Cell Biology 25, no. 12 (2024): 958-978.

[23]

C. A. Schmitt, T. Tchkonia, L. J. Niedernhofer, et al., “COVID-19 and Cellular Senescence,” Nature Reviews Immunology 23, no. 4 (2023): 251-263.

[24]

D. Zhang, G. Chen, D. Manwani, et al., “Neutrophil Ageing Is Regulated by the Microbiome,” Nature 525, no. 7570 (2015): 528-532.

[25]

R. Grieshaber-Bouyer, F. A. Radtke, P. Cunin, et al., “The Neutrotime Transcriptional Signature Defines a Single Continuum of Neutrophils Across Biological Compartments,” Nature Communications 12, no. 1 (2021): 2856.

[26]

C. Silvestre-Roig, Z. G. Fridlender, M. Glogauer, et al., “Neutrophil Diversity in Health and Disease,” Trends in Immunology 40, no. 7 (2019): 565-583.

[27]

S. Devi, Y. Wang, W. K. Chew, et al., “Neutrophil Mobilization via plerixafor-mediated CXCR4 Inhibition Arises From Lung Demargination and Blockade of Neutrophil Homing to the Bone Marrow,” The Journal of Experimental Medicine 210, no. 11 (2013): 2321-2336.

[28]

I. Puga, M. Cols, C. M. Barra, et al., “B Cell-helper Neutrophils Stimulate the Diversification and Production of Immunoglobulin in the Marginal Zone of the Spleen,” Nature Immunology 13, no. 2 (2011): 170-180.

[29]

J. Y. Sagiv, J. Michaeli, S. Assi, et al., “Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer,” Cell Reports 10, no. 4 (2015): 562-573.

[30]

X. Wang, L. Qiu, Z. Li, et al., “Understanding the Multifaceted Role of Neutrophils in Cancer and Autoimmune Diseases,” Frontiers In Immunology 9 (2018): 2456.

[31]

J. Y. Sagiv, S. Voels, and Z. Granot, “Isolation and Characterization of Low- vs. High-Density Neutrophils in Cancer,” Methods in Molecular Biology 1458 (2016): 179-193.

[32]

M.-S. Jan, Y.-H. Huang, B. Shieh, et al., “CC Chemokines Induce Neutrophils to Chemotaxis, Degranulation, and Alpha-defensin Release,” Journal of Acquired Immune Deficiency Syndromes 41, no. 1 (2006): 6-16.

[33]

B. E. Hsu, S. Tabariès, R. M. Johnson, et al., “Immature Low-Density Neutrophils Exhibit Metabolic Flexibility That Facilitates Breast Cancer Liver Metastasis,” Cell Reports 27, no. 13 (2019): 3902-3915.

[34]

S. Trellakis, H. Farjah, K. Bruderek, et al., “Peripheral Blood Neutrophil Granulocytes From Patients With Head and Neck Squamous Cell Carcinoma Functionally Differ From Their Counterparts in Healthy Donors,” International Journal of Immunopathology and Pharmacology 24, no. 3 (2011): 683-693.

[35]

R. Taneja, A. P. Sharma, M. B. Hallett, et al., “Immature Circulating Neutrophils in Sepsis Have Impaired Phagocytosis and Calcium Signaling,” Shock (Augusta, Ga.) 30, no. 6 (2008): 618-622.

[36]

G. Drifte, I. Dunn-Siegrist, P. Tissières, et al., “Innate Immune Functions of Immature Neutrophils in Patients With Sepsis and Severe Systemic Inflammatory Response Syndrome,” Critical Care Medicine 41, no. 3 (2013): 820-832.

[37]

P. Scapini, O. Marini, C. Tecchio, et al., “Human Neutrophils in the Saga of Cellular Heterogeneity: Insights and Open Questions,” Immunological Reviews 273, no. 1 (2016): 48-60.

[38]

N. L. Bowers, E. S. Helton, R. P. H. Huijbregts, et al., “Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 Pathway,” Plos Pathogens 10, no. 3 (2014): e1003993.

[39]

S. Brandau, K. Moses, and S. Lang, “The Kinship of Neutrophils and Granulocytic Myeloid-derived Suppressor Cells in Cancer: Cousins, Siblings or Twins?,” Seminars In Cancer Biology 23, no. 3 (2013): 171-182.

[40]

T. Vollbrecht, R. Stirner, A. Tufman, et al., “Chronic Progressive HIV-1 Infection Is Associated With Elevated Levels of Myeloid-derived Suppressor Cells,” Aids 26, no. 12 (2012): F31-F37.

[41]

E. Eruslanov, M. Neuberger, I. Daurkin, et al., “Circulating and Tumor-infiltrating Myeloid Cell Subsets in Patients With Bladder Cancer,” International Journal of Cancer 130, no. 5 (2012): 1109-1119.

[42]

S. H. Tay, T. Celhar, and A.-M Fairhurst, “Low-Density Neutrophils in Systemic Lupus Erythematosus,” Arthritis Rheumatol 72, no. 10 (2020): 1587-1595.

[43]

M. F. Denny, S. Yalavarthi, W. Zhao, et al., “A Distinct Subset of Proinflammatory Neutrophils Isolated From Patients With Systemic Lupus Erythematosus Induces Vascular Damage and Synthesizes Type I IFNs,” Journal of Immunology 184, no. 6 (2010): 3284-3297.

[44]

C. Lood, L. P. Blanco, M. M. Purmalek, et al., “Neutrophil Extracellular Traps Enriched in Oxidized Mitochondrial DNA Are Interferogenic and Contribute to Lupus-Like Disease,” Nature Medicine 22, no. 2 (2016): 146-153.

[45]

E. Villanueva, S. Yalavarthi, C. C. Berthier, et al., “Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues, and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus,” Journal of Immunology 187, no. 1 (2011): 538-552.

[46]

A. M. Lin, C. J. Rubin, R. Khandpur, et al., “Mast Cells and Neutrophils Release IL-17 Through Extracellular Trap Formation in Psoriasis,” Journal of Immunology 187, no. 1 (2011): 490-500.

[47]

E. Kolaczkowska and P. Kubes, “Neutrophil Recruitment and Function in Health and Inflammation,” Nature Reviews Immunology 13, no. 3 (2013): 159-175.

[48]

A. Zarbock, K. Ley, R. P. McEver, et al., “Leukocyte Ligands for Endothelial Selectins: Specialized Glycoconjugates That Mediate Rolling and Signaling Under Flow,” Blood 118, no. 26 (2011): 6743-6751.

[49]

M. Kowanetz, X. Wu, J. Lee, et al., “Granulocyte-colony Stimulating Factor Promotes Lung Metastasis Through Mobilization of Ly6G+Ly6C+ Granulocytes,” Proceedings of the National Academy of Sciences of the United States of America 107, no. 50 (2010): 21248-21255.

[50]

G. Zuchtriegel, B. Uhl, D. Puhr-Westerheide, et al., “Platelets Guide Leukocytes to Their Sites of Extravasation,” Plos Biology 14, no. 5 (2016): e1002459.

[51]

J. Rossaint, A. Margraf, and A. Zarbock, “Role of Platelets in Leukocyte Recruitment and Resolution of Inflammation,” Frontiers In Immunology 9 (2018): 2712.

[52]

J. Rossaint, K. Kühne, J. Skupski, et al., “Directed Transport of Neutrophil-derived Extracellular Vesicles Enables Platelet-mediated Innate Immune Response,” Nature Communications 7 (2016): 13464.

[53]

K. De Filippo and S. M Rankin, “The Secretive Life of Neutrophils Revealed by Intravital Microscopy,” Frontiers In Cell and Developmental Biology 8 (2020): 603230.

[54]

M. G. Manz and S. Boettcher, “Emergency Granulopoiesis,” Nature Reviews Immunology 14, no. 5 (2014): 302-314.

[55]

Y. Liu, M. R. Smith, Y. Wang, et al., “c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities,” Cancers 15, no. 9 (2023): 2626.

[56]

V. Schimek, K. Strasser, A. Beer, et al., “Tumour Cell Apoptosis Modulates the Colorectal Cancer Immune Microenvironment via Interleukin-8-dependent Neutrophil Recruitment,” Cell death & disease 13, no. 2 (2022): 113.

[57]

Y. Yin, H. Dai, X. Sun, et al., “HRG Inhibits Liver Cancer Lung Metastasis by Suppressing Neutrophil Extracellular Trap Formation,” Clinical and Translational Medicine 13, no. 6 (2023): e1283.

[58]

X. Yu, C. Li, Z. Wang, et al., “Neutrophils in Cancer: Dual Roles Through Intercellular Interactions,” Oncogene 43, no. 16 (2024): 1163-1177.

[59]

Ö. Canli, A. M. Nicolas, J. Gupta, et al., “Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis,” Cancer Cell 32, no. 6 (2017): 869-883.

[60]

M. Gershkovitz, Y. Caspi, T. Fainsod-Levi, et al., “TRPM2 Mediates Neutrophil Killing of Disseminated Tumor Cells,” Cancer Research 78, no. 10 (2018): 2680-2690.

[61]

H. L. Matlung, L. Babes, X. W. Zhao, et al., “Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis,” Cell Reports 23, no. 13 (2018): 3946-3959.

[62]

J. Pillay, I. den Braber, N. Vrisekoop, et al., “In Vivo Labeling With 2H2O Reveals a human Neutrophil Lifespan of 5.4 Days,” Blood 116, no. 4 (2010): 625-627.

[63]

J. Lahoz-Beneytez, M. Elemans, Y. Zhang, et al., “Human Neutrophil Kinetics: Modeling of Stable Isotope Labeling Data Supports Short Blood Neutrophil Half-lives,” Blood 127, no. 26 (2016): 3431-3438.

[64]

S. Liu, W. Wu, Y. Du, et al., “The Evolution and Heterogeneity of Neutrophils in Cancers: Origins, Subsets, Functions, Orchestrations and Clinical Applications,” Molecular cancer 22, no. 1 (2023): 148.

[65]

E. Pérez-Figueroa, P. Álvarez-Carrasco, E. Ortega, et al., “Neutrophils: Many Ways to Die,” Frontiers In Immunology 12 (2021): 631821.

[66]

J. Vier, M. Groth, M. Sochalska, et al., “The Anti-apoptotic Bcl-2 family Protein A1/Bfl-1 Regulates Neutrophil Survival and Homeostasis and Is Controlled via PI3K and JAK/STAT Signaling,” Cell Death & Disease 7, no. 2 (2016): e2103.

[67]

P. R. Webb, K. Q. Wang, D. Scheel-Toellner, et al., “Regulation of Neutrophil Apoptosis: A Role for Protein Kinase C and Phosphatidylinositol-3-kinase,” Apoptosis 5, no. 5 (2000): 451-458.

[68]

R. Kettritz, M. L. Gaido, H. Haller, et al., “Interleukin-8 Delays Spontaneous and Tumor Necrosis Factor-alpha-mediated Apoptosis of human Neutrophils,” Kidney International 53, no. 1 (1998): 84-91.

[69]

J. M. van den Berg, S. Weyer, J. J. Weening, et al., “Divergent Effects of Tumor Necrosis Factor Alpha on Apoptosis of human Neutrophils,” Journal of Leukocyte Biology 69, no. 3 (2001): 467-473.

[70]

F. Colotta, F. Re, N. Polentarutti, et al., “Modulation of Granulocyte Survival and Programmed Cell Death by Cytokines and Bacterial Products,” Blood 80, no. 8 (1992): 2012-2020.

[71]

A. Singh and N. Rieber, “In Vitro Generation of Human Neutrophilic Myeloid-Derived Suppressor Cells,” Methods in Molecular Biology 2236 (2021): 77-83.

[72]

C. B. Caspar, R. A. Seger, J. Burger, et al., “Effective Stimulation of Donors for Granulocyte Transfusions With Recombinant Methionyl Granulocyte Colony-stimulating Factor,” Blood 81, no. 11 (1993): 2866-2871.

[73]

Y. Yu and B. Sun, “Autophagy-mediated Regulation of Neutrophils and Clinical Applications,” Burns Trauma 8 (2020): tkz001.

[74]

M. Qian, X. Fang, and X. Wang, “Autophagy and Inflammation,” Clinical and Translational Medicine 6, no. 1 (2017): 24.

[75]

J. Hughes, R. J. Johnson, A. Mooney, et al., “Neutrophil Fate in Experimental Glomerular Capillary Injury in the Rat. Emigration Exceeds in Situ Clearance by Apoptosis,” American Journal of Pathology 150, no. 1 (1997): 223-234.

[76]

Q. Xu, W. Zhao, M. Yan, et al., “Neutrophil Reverse Migration,” J Inflamm (Lond) 19, no. 1 (2022): 22.

[77]

S. de Oliveira, E. E. Rosowski, and A. Huttenlocher, “Neutrophil Migration in Infection and Wound Repair: Going Forward in Reverse,” Nature Reviews Immunology 16, no. 6 (2016): 378-391.

[78]

P. Cech and R. I Lehrer, “Heterogeneity of human Neutrophil Phagolysosomes: Functional Consequences for Candidacidal Activity,” Blood 64, no. 1 (1984): 147-151.

[79]

P. T. King and L. Dousha, “Neutrophil Extracellular Traps and Respiratory Disease,” Journal of Clinical Medicine 13, no. 8 (2024).

[80]

H. Aegerter, B. N. Lambrecht, and C. V Jakubzick, “Biology of Lung Macrophages in Health and Disease,” Immunity 55, no. 9 (2022): 1564-1580.

[81]

A. Mócsai, “Diverse Novel Functions of Neutrophils in Immunity, Inflammation, and Beyond,” The Journal of Experimental Medicine 210, no. 7 (2013): 1283-1299.

[82]

J. B. Cowland and N. Borregaard, “Granulopoiesis and Granules of human Neutrophils,” Immunological Reviews 273, no. 1 (2016): 11-28.

[83]

Y. Liang, G. Wu, J. Tan, et al., “Targeting NETosis: Nature's Alarm System in Cancer Progression,” Cancer Drug Resist 7 (2024): 28.

[84]

P. Nordenfelt and H. Tapper, “Phagosome Dynamics During Phagocytosis by Neutrophils,” Journal of Leukocyte Biology 90, no. 2 (2011): 271-284.

[85]

K. D. Metzler, C. Goosmann, A. Lubojemska, et al., “A Myeloperoxidase-containing Complex Regulates Neutrophil Elastase Release and Actin Dynamics During NETosis,” Cell Reports 8, no. 3 (2014): 883-896.

[86]

P. Van Lint and C. Libert, “Chemokine and Cytokine Processing by Matrix Metalloproteinases and Its Effect on Leukocyte Migration and Inflammation,” Journal of Leukocyte Biology 82, no. 6 (2007): 1375-1381.

[87]

A. Aguirre, J. Blázquez-Prieto, L. Amado-Rodriguez, et al., “Matrix Metalloproteinase-14 Triggers an Anti-inflammatory Proteolytic Cascade in Endotoxemia,” J Mol Med (Berl) 95, no. 5 (2017): 487-497.

[88]

B. Cauwe, E. Martens, P. Proost, et al., “Multidimensional Degradomics Identifies Systemic Autoantigens and Intracellular Matrix Proteins as Novel Gelatinase B/MMP-9 Substrates,” Integr Biol (Camb) 1, no. 5-6 (2009): 404-426.

[89]

V. Brinkmann, U. Reichard, C. Goosmann, et al., “Neutrophil Extracellular Traps Kill Bacteria,” Science 303, no. 5663 (2004): 1532-1535.

[90]

J. Wu, W. Dong, Y. Pan, et al., “Crosstalk Between Gut Microbiota and Metastasis in Colorectal Cancer: Implication of Neutrophil Extracellular Traps,” Frontiers in immunology 14 (2023): 1296783.

[91]

J. Huang, W. Hong, M. Wan, et al., “Molecular Mechanisms and Therapeutic Target of NETosis in Diseases,” MedComm 3, no. 3 (2022): e162.

[92]

M. Herre, J. Cedervall, N. Mackman, et al., “Neutrophil Extracellular Traps in the Pathology of Cancer and Other Inflammatory Diseases,” Physiological Reviews 103, no. 1 (2023): 277-312.

[93]

B. J. Barnes, J. M. Adrover, A. Baxter-Stoltzfus, et al., “Targeting Potential Drivers of COVID-19: Neutrophil Extracellular Traps,” The Journal of Experimental Medicine 217, no. 6 (2020): e20200652.

[94]

S. R. Clark, A. C. Ma, S. A. Tavener, et al., “Platelet TLR4 Activates Neutrophil Extracellular Traps to Ensnare Bacteria in Septic Blood,” Nature Medicine 13, no. 4 (2007): 463-469.

[95]

T. A. Fuchs, A. Brill, D. Duerschmied, et al., “Extracellular DNA Traps Promote Thrombosis,” Proceedings of the National Academy of Sciences of the United States of America 107, no. 36 (2010): 15880-15885.

[96]

L. Camous, L. Roumenina, S. Bigot, et al., “Complement Alternative Pathway Acts as a Positive Feedback Amplification of Neutrophil Activation,” Blood 117, no. 4 (2011): 1340-1349.

[97]

C. Nathan, “Neutrophils and Immunity: Challenges and Opportunities,” Nature Reviews Immunology 6, no. 3 (2006): 173-182.

[98]

S. A. Rizo-Téllez and J. G Filep, “Beyond Host Defense and Tissue Injury: The Emerging Role of Neutrophils in Tissue Repair,” American Journal of Physiology. Cell Physiology 326, no. 3 (2024): C661-c683.

[99]

A. D. Gregory, C. R. Kliment, H. E. Metz, et al., “Neutrophil Elastase Promotes Myofibroblast Differentiation in Lung Fibrosis,” Journal of Leukocyte Biology 98, no. 2 (2015): 143-152.

[100]

R. M. Devalaraja, L. B. Nanney, J. Du, et al., “Delayed Wound Healing in CXCR2 Knockout Mice,” Journal of Investigative Dermatology 115, no. 2 (2000): 234-244.

[101]

V. C. Ardi, T. A. Kupriyanova, E. I. Deryugina, et al., “Human Neutrophils Uniquely Release TIMP-free MMP-9 to Provide a Potent Catalytic Stimulator of Angiogenesis,” Proceedings of the National Academy of Sciences of the United States of America 104, no. 51 (2007): 20262-20267.

[102]

K. J. Greenlee, Z. Werb, and F. Kheradmand, “Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted,” Physiological Reviews 87, no. 1 (2007): 69-98.

[103]

A. Fischer, J. Wannemacher, S. Christ, et al., “Neutrophils Direct Preexisting Matrix to Initiate Repair in Damaged Tissues,” Nature Immunology 23, no. 4 (2022): 518-531.

[104]

M. J. Daseke, F. M. Valerio, W. J. Kalusche, et al., “Neutrophil Proteome Shifts Over the Myocardial Infarction Time Continuum,” Basic Research in Cardiology 114, no. 5 (2019): 37.

[105]

S. Kumaran Satyanarayanan, D. El Kebir, S. Soboh, et al., “IFN-β Is a Macrophage-derived Effector Cytokine Facilitating the Resolution of Bacterial Inflammation,” Nature Communications 10, no. 1 (2019): 3471.

[106]

A. C. Doran, A. Yurdagul, and I. Tabas, “Efferocytosis in Health and Disease,” Nature Reviews Immunology 20, no. 4 (2020): 254-267.

[107]

S. Morioka, C. Maueröder, and K. S Ravichandran, “Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology,” Immunity 50, no. 5 (2019): 1149-1162.

[108]

J. A. Lindborg, M. Mack, and R. E Zigmond, “Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration,” Journal of Neuroscience 37, no. 43 (2017): 10258-10277.

[109]

N. Borregaard and T. Herlin, “Energy Metabolism of human Neutrophils During Phagocytosis,” The Journal of Clinical Investigation 70, no. 3 (1982): 550-557.

[110]

S. Peng, J. Gao, D. Stojkov, et al., “Established and Emerging Roles for Mitochondria in Neutrophils,” Immunological Reviews 314, no. 1 (2023): 413-426.

[111]

P. Ettel and T. Weichhart, “Not Just Sugar: Metabolic Control of Neutrophil Development and Effector Functions,” J Leukoc Biol 116, no. 3 (2024): 487-510.

[112]

A. Shafqat, J. A. Khan, A. Y. Alkachem, et al., “How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease,” International Journal of Molecular Sciences 24, no. 24 (2023): 17583.

[113]

L. Mohammadnezhad, M. Shekarkar Azgomi, M. P. La Manna, et al., “Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in,” Autoimmunity Cells 11, no. 10 (2022): 1663.

[114]

N. Lin and M. C Simon, “Hypoxia-inducible Factors: Key Regulators of Myeloid Cells During Inflammation,” The Journal of Clinical Investigation 126, no. 10 (2016): 3661-3671.

[115]

T. Liu, L. Zhang, D. Joo, et al., “NF-κB Signaling in Inflammation,” Signal Transduct Target Ther 2 (2017): 17023-17023.

[116]

M. Mussbacher, M. Salzmann, C. Brostjan, et al., “Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis,” Frontiers In Immunology 10 (2019): 85.

[117]

A. Itakura and O. J. T McCarty, “Pivotal Role for the mTOR Pathway in the Formation of Neutrophil Extracellular Traps via Regulation of Autophagy,” American Journal of Physiology Cell Physiology 305, no. 3 (2013): C348-C354.

[118]

C. L. Stothers, L. Luan, B. A. Fensterheim, et al., “Hypoxia-inducible Factor-1α Regulation of Myeloid Cells,” J Mol Med (Berl) 96, no. 12 (2018): 1293-1306.

[119]

G. Zhong, Y. Guo, X. Gong, et al., “Enhanced Glycolysis by ATPIF1 Gene Inactivation Increased the Anti-bacterial Activities of Neutrophils Through Induction of ROS and Lactic Acid,” Biochim Biophys Acta Mol Basis Dis 1869, no. 8 (2023): 166820.

[120]

C. T. Taylor and S. P Colgan, “Regulation of Immunity and Inflammation by Hypoxia in Immunological Niches,” Nature Reviews Immunology 17, no. 12 (2017): 774-785.

[121]

N. Borregaard, J. H. Schwartz, and A. I Tauber, “Proton Secretion by Stimulated Neutrophils. Significance of Hexose Monophosphate Shunt Activity as Source of Electrons and Protons for the respiratory Burst,” The Journal of Clinical Investigation 74, no. 2 (1984): 455-459.

[122]

A. Shafqat, S. Abdul Rab, O. Ammar, et al., “Emerging Role of Neutrophil Extracellular Traps in the Complications of Diabetes Mellitus,” Front Med (Lausanne) 9 (2022): 995993.

[123]

L. Wang, X. Zhou, Y. Yin, et al., “Hyperglycemia Induces Neutrophil Extracellular Traps Formation through an NADPH Oxidase-Dependent Pathway in Diabetic Retinopathy,” Frontiers In Immunology 9 (2018): 3076.

[124]

I. Kaymak, K. M. Luda, L. R. Duimstra, et al., “Carbon Source Availability Drives Nutrient Utilization in CD8+ T Cells,” Cell metabolism 34, no. 9 (2022): 1298-1311.

[125]

J. Ma, L. Tang, Y. Tan, et al., “Lithium Carbonate Revitalizes Tumor-reactive CD8+ T Cells by Shunting Lactic Acid Into Mitochondria,” Nature Immunology 25, no. 3 (2024): 552-561.

[126]

P. Sadiku, J. A. Willson, E. M. Ryan, et al., “Neutrophils Fuel Effective Immune Responses Through Gluconeogenesis and Glycogenesis,” Cell metabolism 33, no. 2 (2021): 411-423.

[127]

T. C. Pithon-Curi, M. P. De Melo, and R. Curi, “Glucose and Glutamine Utilization by Rat Lymphocytes, Monocytes and Neutrophils in Culture: A Comparative Study,” Cell Biochemistry and Function 22, no. 5 (2004): 321-326.

[128]

T. C. Pithon-Curi, A. G. Trezena, W. Tavares-Lima, et al., “Evidence That Glutamine Is Involved in Neutrophil Function,” Cell Biochemistry and Function 20, no. 2 (2002): 81-86.

[129]

J.-H. Jeon, C.-W. Hong, E. Y. Kim, et al., “Current Understanding on the Metabolism of Neutrophils,” Immune Netw 20, no. 6 (2020): e46.

[130]

R. Curi, A. C. Levada-Pires, E. B. d Silva, et al., “The Critical Role of Cell Metabolism for Essential Neutrophil Functions,” Cellular Physiology and Biochemistry 54, no. 4 (2020): 629-647.

[131]

H. Yoon, J. L. Shaw, M. C. Haigis, et al., “Lipid Metabolism in Sickness and in Health: Emerging Regulators of Lipotoxicity,” Molecular Cell 81, no. 18 (2021): 3708-3730.

[132]

C. P. Burns, I. R. Welshman, and A. A Spector, “Differences in Free Fatty Acid and Glucose Metabolism of human Blood Neutrophils and Lymphocytes,” Blood 47, no. 3 (1976): 431-437.

[133]

P. F. Weller, S. J. Ackerman, A. Nicholson-Weller, et al., “Cytoplasmic Lipid Bodies of human Neutrophilic Leukocytes,” American Journal of Pathology 135, no. 5 (1989): 947-959.

[134]

L. L. Lara, H. Rivera, C. Perez-P, et al., “Low Density Lipoprotein Receptor Expression and Function in human Polymorphonuclear Leucocytes,” Clinical and Experimental Immunology 107, no. 1 (1997): 205-212.

[135]

S. Jaillon, A. Ponzetta, D. Di Mitri, et al., “Neutrophil Diversity and Plasticity in Tumour Progression and Therapy,” Nature Reviews Cancer 20, no. 9 (2020): 485-503.

[136]

Z. G. Fridlender, J. Sun, S. Kim, et al., “Polarization of Tumor-associated Neutrophil Phenotype by TGF-beta: “N1” versus “N2” TAN,” Cancer Cell 16, no. 3 (2009): 183-194.

[137]

S. Yang, J. Jia, F. Wang, et al., “Targeting Neutrophils: Mechanism and Advances in Cancer Therapy,” Clinical and translational medicine 14, no. 3 (2024): e1599.

[138]

X. Huang, E. Nepovimova, V. Adam, et al., “Neutrophils in Cancer Immunotherapy: Friends or Foes?,” Molecular cancer 23, no. 1 (2024): 107.

[139]

T. Liu, S. Zong, Y. Jiang, et al., “Neutrophils Promote Larynx Squamous Cell Carcinoma Progression via Activating the IL-17/JAK/STAT3 Pathway,” Journal of Immunology Research 2021 (2021): 8078646.

[140]

W. Zhou, X. Cao, Q. Xu, et al., “The Double-edged Role of Neutrophil Heterogeneity in Inflammatory Diseases and Cancers,” MedComm 4, no. 4 (2023): e325.

[141]

A. Mantovani, M. A. Cassatella, C. Costantini, et al., “Neutrophils in the Activation and Regulation of Innate and Adaptive Immunity,” Nature Reviews Immunology 11, no. 8 (2011): 519-531.

[142]

Y. Koga, A. Matsuzaki, A. Suminoe, et al., “Neutrophil-derived TNF-related Apoptosis-inducing Ligand (TRAIL): A Novel Mechanism of Antitumor Effect by Neutrophils,” Cancer Research 64, no. 3 (2004): 1037-1043.

[143]

C. Cui, K. Chakraborty, X. A. Tang, et al., “Neutrophil Elastase Selectively Kills Cancer Cells and Attenuates Tumorigenesis,” Cell 184, no. 12 (2021): 3163-3177.

[144]

B. Sun, W. Qin, M. Song, et al., “Neutrophil Suppresses Tumor Cell Proliferation via Fas /Fas Ligand Pathway Mediated Cell Cycle Arrested,” Int J Biol Sci 14, no. 14 (2018): 2103-2113.

[145]

K. Mahiddine, A. Blaisdell, S. Ma, et al., “Relief of Tumor Hypoxia Unleashes the Tumoricidal Potential of Neutrophils,” The Journal of Clinical Investigation 130, no. 1 (2020): 389-403.

[146]

C. L. Chen, Y. Wang, C. Y. Huang, et al., “IL-17 Induces Antitumor Immunity by Promoting Beneficial Neutrophil Recruitment and Activation in Esophageal Squamous Cell Carcinoma,” Oncoimmunology 7, no. 1 (2017): e1373234.

[147]

Z. Zhang, R. Niu, L. Zhao, et al., “Mechanisms of Neutrophil Extracellular Trap Formation and Regulation in Cancers,” International Journal of Molecular Sciences 24, no. 12 (2023): 10265.

[148]

D. Hirschhorn, S. Budhu, L. Kraehenbuehl, et al., “T Cell Immunotherapies Engage Neutrophils to Eliminate Tumor Antigen Escape Variants,” Cell 186, no. 7 (2023): 1432-1447. e1417.

[149]

E. Pylaeva, G. Korschunow, I. Spyra, et al., “During Early Stages of Cancer, Neutrophils Initiate Anti-tumor Immune Responses in Tumor-draining Lymph Nodes,” Cell Reports 40, no. 7 (2022): 111171.

[150]

J. Gungabeesoon, N. A. Gort-Freitas, M. Kiss, et al., “A Neutrophil Response Linked to Tumor Control in Immunotherapy,” Cell 186, no. 7 (2023): 1448-1464. e1420.

[151]

S. E. Erdman, V. P. Rao, T. Poutahidis, et al., “Nitric Oxide and TNF-alpha Trigger Colonic Inflammation and Carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient Mice,” PNAS 106, no. 4 (2009): 1027-1032.

[152]

S. Xiong, L. Dong, and L. Cheng, “Neutrophils in Cancer Carcinogenesis and Metastasis,” Journal of hematology & oncology 14, no. 1 (2021): 173.

[153]

S. Jaillon, A. Ponzetta, D. Di Mitri, et al., “Neutrophil Diversity and Plasticity in Tumour Progression and Therapy,” Nature Reviews Cancer 20, no. 9 (2020): 485-503.

[154]

S. Tohme, H. O. Yazdani, A.l-K. AB, et al., “Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases After Surgical Stress,” Cancer Research 76, no. 6 (2016): 1367-1380.

[155]

M. L. De Meo and J. D Spicer, “The Role of Neutrophil Extracellular Traps in Cancer Progression and Metastasis,” Seminars In Immunology 57 (2021): 101595.

[156]

F. Liu, H. Y. Wu, R. Wesselschmidt, et al., “Impaired Production and Increased Apoptosis of Neutrophils in Granulocyte Colony-stimulating Factor Receptor-deficient Mice,” Immunity 5, no. 5 (1996): 491-501.

[157]

L. P. Stabile, J. S. Lyker, S. R. Land, et al., “Transgenic Mice Overexpressing Hepatocyte Growth Factor in the Airways Show Increased Susceptibility to Lung Cancer,” Carcinogenesis 27, no. 8 (2006): 1547-1555.

[158]

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.

[159]

M. M. Queen, R. E. Ryan, R. G. Holzer, et al., “Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression,” Cancer Research 65, no. 19 (2005): 8896-8904.

[160]

R. M. Strieter, M. D. Burdick, B. N. Gomperts, et al., “CXC Chemokines in Angiogenesis,” Cytokine & Growth Factor Reviews 16, no. 6 (2005): 593-609.

[161]

J. Korbecki, K. Kojder, P. Kapczuk, et al., “The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature,” International Journal of Molecular Sciences 22, no. 2 (2021): 843.

[162]

N. N. Pavlova, J. Zhu, and C. B Thompson, “The Hallmarks of Cancer Metabolism: Still Emerging,” Cell metabolism 34, no. 3 (2022): 355-377.

[163]

D. Hanahan, “Hallmarks of Cancer: New Dimensions,” Cancer Discovery 12, no. 1 (2022): 31-46.

[164]

S. Huang, J. Shi, J. Shen, et al., “Metabolic Reprogramming of Neutrophils in the Tumor Microenvironment: Emerging Therapeutic Targets,” Cancer Letters 612 (2025): 217466.

[165]

S. R. Walmsley, C. Print, N. Farahi, et al., “Hypoxia-induced Neutrophil Survival Is Mediated by HIF-1alpha-dependent NF-kappaB Activity,” The Journal of Experimental Medicine 201, no. 1 (2005): 105-115.

[166]

A. Ugolini, A. De Leo, X. Yu, et al., “Functional Reprogramming of Neutrophils Within the Brain Tumor Microenvironment by Hypoxia-driven Histone Lactylation,” Cancer Discovery 15, no. 6 (2025): 1270-1296.

[167]

L. Wang, Y. Liu, Y. Dai, et al., “Single-cell RNA-seq Analysis Reveals BHLHE40-driven Pro-tumour Neutrophils With Hyperactivated Glycolysis in Pancreatic Tumour Microenvironment,” Gut 72, no. 5 (2023): 958-971.

[168]

D. G. Mashek and R. A Coleman, “Cellular Fatty Acid Uptake: The Contribution of Metabolism,” Current Opinion in Lipidology 17, no. 3 (2006): 274-278.

[169]

Z. Gong, Q. Li, J. Shi, et al., “Immunosuppressive Reprogramming of Neutrophils by Lung Mesenchymal Cells Promotes Breast Cancer Metastasis,” Science Immunology 8, no. 80 (2023): eadd5204.

[170]

P. Li, M. Lu, J. Shi, et al., “Dual Roles of Neutrophils in Metastatic Colonization Are Governed by the Host NK Cell Status,” Nature Communications 11, no. 1 (2020): 4387.

[171]

M. E. Shaul, A. Zlotnik, E. Tidhar, et al., “Tumor-Associated Neutrophils Drive B-cell Recruitment and Their Differentiation to Plasma Cells,” Cancer immunology research 9, no. 7 (2021): 811-824.

[172]

C. A. Dumitru, K. Moses, S. Trellakis, et al., “Neutrophils and Granulocytic Myeloid-derived Suppressor Cells: Immunophenotyping, Cell Biology and Clinical Relevance in human Oncology,” Cancer Immunology, Immunotherapy 61, no. 8 (2012): 1155-1167.

[173]

C. M. Rice, L. C. Davies, J. J. Subleski, et al., “Tumour-elicited Neutrophils Engage Mitochondrial Metabolism to Circumvent Nutrient Limitations and Maintain Immune Suppression,” Nature Communications 9, no. 1 (2018): 5099.

[174]

Y. Jo, J. A. Shim, J. W. Jeong, et al., “Targeting ROS-sensing Nrf2 Potentiates Anti-tumor Immunity of Intratumoral CD8+ T and CAR-T Cells,” Molecular Therapy 32, no. 11 (2024): 3879-3894.

[175]

T.-T. Wang, Y.-L. Zhao, L.-S. Peng, et al., “Tumour-activated Neutrophils in Gastric Cancer Foster Immune Suppression and Disease Progression Through GM-CSF-PD-L1 Pathway,” Gut 66, no. 11 (2017): 1900-1911.

[176]

Á. Teijeira, S. Garasa, M. Gato, et al., “CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps That Interfere With Immune Cytotoxicity,” Immunity 52, no. 5 (2020): 856-871. e858.

[177]

F. Veglia, M. Perego, and D. Gabrilovich, “Myeloid-derived Suppressor Cells Coming of Age,” Nature Immunology 19, no. 2 (2018): 108-119.

[178]

T. Condamine, I. Ramachandran, J. I. Youn, et al., “Regulation of Tumor Metastasis by Myeloid-derived Suppressor Cells,” Annual Review of Medicine 66 (2015): 97-110.

[179]

F. Veglia, A. Hashimoto, H. Dweep, et al., “Analysis of Classical Neutrophils and Polymorphonuclear Myeloid-derived Suppressor Cells in Cancer Patients and Tumor-bearing Mice,” Journal of Experimental Medicine 218, no. 4 (2021): e20201803.

[180]

P. Sinha, V. K. Clements, S. K. Bunt, et al., “Cross-talk Between Myeloid-derived Suppressor Cells and Macrophages Subverts Tumor Immunity Toward a Type 2 Response,” Journal of Immunology 179, no. 2 (2007): 977-983.

[181]

D. Bausch, T. Pausch, T. Krauss, et al., “Neutrophil Granulocyte Derived MMP-9 Is a VEGF Independent Functional Component of the Angiogenic Switch in Pancreatic Ductal Adenocarcinoma,” Angiogenesis 14, no. 3 (2011): 235-243.

[182]

A. Spiegel, M. W. Brooks, S. Houshyar, et al., “Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells,” Cancer Discovery 6, no. 6 (2016): 630-649.

[183]

R. Kim, A. Hashimoto, N. Markosyan, et al., “Ferroptosis of Tumour Neutrophils Causes Immune Suppression in Cancer,” Nature 612, no. 7939 (2022): 338-346.

[184]

X. Zhu, W. Zheng, X. Wang, et al., “Enhanced Photodynamic Therapy Synergizing With Inhibition of Tumor Neutrophil Ferroptosis Boosts Anti-PD-1 Therapy of Gastric Cancer,” Adv Sci (Weinh) 11, no. 12 (2024): e2307870.

[185]

F. Veglia, V. A. Tyurin, M. Blasi, et al., “Fatty Acid Transport Protein 2 Reprograms Neutrophils in Cancer,” Nature 569, no. 7754 (2019): 73-78.

[186]

E. Chen and J. Yu, “The Role and Metabolic Adaptations of Neutrophils in Premetastatic Niches,” Biomarker Research 11, no. 1 (2023): 50.

[187]

R. N. Kaplan, R. D. Riba, S. Zacharoulis, et al., “VEGFR1-positive Haematopoietic Bone Marrow Progenitors Initiate the Pre-metastatic Niche,” Nature 438, no. 7069 (2005): 820-827.

[188]

X. Xing, Y. Bai, and J. Song, “The Heterogeneity of Neutrophil Recruitment in the Tumor Microenvironment and the Formation of Premetastatic Niches,” Journal of Immunology Research 2021 (2021): 6687474.

[189]

J. M. Adrover, S. A. C. McDowell, X. Y. He, et al., “NETworking With Cancer: The Bidirectional Interplay Between Cancer and Neutrophil Extracellular Traps,” Cancer Cell 41, no. 3 (2023): 505-526.

[190]

C.-F. Wu, L. Andzinski, N. Kasnitz, et al., “The Lack of Type I Interferon Induces Neutrophil-mediated Pre-metastatic Niche Formation in the Mouse Lung,” International Journal of Cancer 137, no. 4 (2015): 837-847.

[191]

S. K. Wculek and I. Malanchi, “Neutrophils Support Lung Colonization of Metastasis-initiating Breast Cancer Cells,” Nature 528, no. 7582 (2015): 413-417.

[192]

P. F. Yu, Y. Huang, Y. Y. Han, et al., “TNFα-activated Mesenchymal Stromal Cells Promote Breast Cancer Metastasis by Recruiting CXCR2+ Neutrophils,” Oncogene 36, no. 4 (2017): 482-490.

[193]

A. Müller, B. Homey, H. Soto, et al., “Involvement of Chemokine Receptors in Breast Cancer Metastasis,” Nature 410, no. 6824 (2001): 50-56.

[194]

B. Hermant, S. Bibert, E. Concord, et al., “Identification of Proteases Involved in the Proteolysis of Vascular Endothelium Cadherin During Neutrophil Transmigration,” Journal of Biological Chemistry 278, no. 16 (2003): 14002-14012.

[195]

A. Tyagi, S. Sharma, K. Wu, et al., “Nicotine Promotes Breast Cancer Metastasis by Stimulating N2 Neutrophils and Generating Pre-metastatic Niche in Lung,” Nature Communications 12, no. 1 (2021): 474.

[196]

W. Lee, S. Y. Ko, M. S. Mohamed, et al., “Neutrophils Facilitate Ovarian Cancer Premetastatic Niche Formation in the Omentum,” Journal of Experimental Medicine 216, no. 1 (2019): 176-194.

[197]

M. McCourt, J. H. Wang, S. Sookhai, et al., “Proinflammatory Mediators Stimulate Neutrophil-directed Angiogenesis,” Archives of Surgery 134, no. 12 (1999): 1325-1332.

[198]

S. Tohme, H. O. Yazdani, A. B. Al-Khafaji, et al., “Neutrophil Extracellular Traps Promote the Development and Progression of Liver Metastases After Surgical Stress,” Cancer Research 76, no. 6 (2016): 1367-1380.

[199]

S. Najmeh, J. Cools-Lartigue, R. F. Rayes, et al., “Neutrophil Extracellular Traps Sequester Circulating Tumor Cells via β1-integrin Mediated Interactions,” International Journal of Cancer 140, no. 10 (2017): 2321-2330.

[200]

A. W. Lambert, D. R. Pattabiraman, and R. A Weinberg, “Emerging Biological Principles of Metastasis,” Cell 168, no. 4 (2017): 670-691.

[201]

L.-Y. Yang, Q. Luo, L. Lu, et al., “Increased Neutrophil Extracellular Traps Promote Metastasis Potential of Hepatocellular Carcinoma via Provoking Tumorous Inflammatory Response,” Journal of Hematology & Oncology 13, no. 1 (2020): 3.

[202]

L. Yang, L. Liu, R. Zhang, et al., “IL-8 Mediates a Positive Loop Connecting Increased Neutrophil Extracellular Traps (NETs) and Colorectal Cancer Liver Metastasis,” Journal of Cancer 11, no. 15 (2020): 4384-4396.

[203]

J. Park, R. W. Wysocki, Z. Amoozgar, et al., “Cancer Cells Induce Metastasis-supporting Neutrophil Extracellular DNA Traps,” Science Translational Medicine 8, no. 361 (2016): 361ra138.

[204]

C. Engblom, C. Pfirschke, R. Zilionis, et al., “Osteoblasts Remotely Supply Lung Tumors With Cancer-promoting SiglecF(high) Neutrophils,” Science 358, no. 6367 (2017): eaal5081.

[205]

M. J. Topper, M. Vaz, K. A. Marrone, et al., “The Emerging Role of Epigenetic Therapeutics in Immuno-oncology,” Nature Reviews Clinical Oncology 17, no. 2 (2020): 75-90.

[206]

J. Yao, L. Ji, G. Wang, et al., “Effect of Neutrophils on Tumor Immunity and Immunotherapy Resistance With Underlying Mechanisms,” Cancer Commun (Lond) 45, no. 1 (2025): 15-42.

[207]

Y. Zhou, C. Na, and Z. Li, “Novel Insights Into Immune Cells Modulation of Tumor Resistance,” Critical Reviews in Oncology/Hematology 202 (2024): 104457.

[208]

H. Liu, H. Zhao, M. Zhou, et al., “Neutrophils in Cancer Drug Resistance: Roles and Therapeutic Opportunities,” Cancer Letters 611 (2024): 217417.

[209]

T. Hideshima, N. Nakamura, D. Chauhan, et al., “Biologic Sequelae of Interleukin-6 Induced PI3-K/Akt Signaling in Multiple Myeloma,” Oncogene 20, no. 42 (2001): 5991-6000.

[210]

I. R. Ramachandran, T. Condamine, C. Lin, et al., “Bone Marrow PMN-MDSCs and Neutrophils Are Functionally Similar in Protection of Multiple Myeloma From Chemotherapy,” Cancer Letters 371, no. 1 (2016): 117-124.

[211]

Y. Wang, X. L. Niu, Y. Qu, et al., “Autocrine Production of Interleukin-6 Confers Cisplatin and Paclitaxel Resistance in Ovarian Cancer Cells,” Cancer Letters 295, no. 1 (2010): 110-123.

[212]

G. W. Prager, J. Taieb, M. Fakih, et al., “Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer,” New England Journal of Medicine 388, no. 18 (2023): 1657-1667.

[213]

M. Omatsu, Y. Nakanishi, K. Iwane, et al., “THBS1-producing Tumor-infiltrating Monocyte-Like Cells Contribute to Immunosuppression and Metastasis in Colorectal Cancer,” Nature Communications 14, no. 1 (2023): 5534.

[214]

H. Arasanz, A. I. Bocanegra, I. Morilla, et al., “Circulating Low Density Neutrophils Are Associated With Resistance to First Line Anti-PD1/PDL1 Immunotherapy in Non-Small Cell Lung Cancer,” Cancers 14, no. 16 (2022): 3846.

[215]

W. Song, L. Li, D. He, et al., “Infiltrating Neutrophils Promote Renal Cell Carcinoma (RCC) Proliferation via Modulating Androgen Receptor (AR) → c-Myc Signals,” Cancer Letters 368, no. 1 (2015): 71-78.

[216]

T. M. Bui, V. Butin-Israeli, H. L. Wiesolek, et al., “Neutrophils Alter DNA Repair Landscape to Impact Survival and Shape Distinct Therapeutic Phenotypes of Colorectal Cancer,” Gastroenterology 161, no. 1 (2021): 225-238.

[217]

Y. Wang, Q. Zhao, B. Zhao, et al., “Remodeling Tumor-Associated Neutrophils to Enhance Dendritic Cell-Based HCC Neoantigen Nano-Vaccine Efficiency,” Adv Sci (Weinh) 9, no. 11 (2022): e2105631.

[218]

S. Shinde-Jadhav, J. J. Mansure, R. F. Rayes, et al., “Role of Neutrophil Extracellular Traps in Radiation Resistance of Invasive Bladder Cancer,” Nature Communications 12, no. 1 (2021): 2776.

[219]

H. Wang, H. Zhang, Y. Wang, et al., “Regulatory T-cell and Neutrophil Extracellular Trap Interaction Contributes to Carcinogenesis in Non-alcoholic Steatohepatitis,” Journal of Hepatology 75, no. 6 (2021): 1271-1283.

[220]

C. Kaltenmeier, H. O. Yazdani, K. Morder, et al., “Neutrophil Extracellular Traps Promote T Cell Exhaustion in the Tumor Microenvironment,” Frontiers In Immunology 12 (2021): 785222.

[221]

A. Mousset, E. Lecorgne, I. Bourget, et al., “Neutrophil Extracellular Traps Formed During Chemotherapy Confer Treatment Resistance via TGF-β Activation,” Cancer Cell 41, no. 4 (2023): 757-775.

[222]

A. Mousset, L. Bellone, C. Gaggioli, et al., “NETscape or NEThance: Tailoring Anti-cancer Therapy,” Trends in cancer 10, no. 7 (2024): 655-667.

[223]

T. Takeshima, L. M. Pop, A. Laine, et al., “Key Role for Neutrophils in Radiation-induced Antitumor Immune Responses: Potentiation With G-CSF,” PNAS 113, no. 40 (2016): 11300-11305.

[224]

A. J. Wisdom, C. S. Hong, A. J. Lin, et al., “Neutrophils Promote Tumor Resistance to Radiation Therapy,” PNAS 116, no. 37 (2019): 18584-18589.

[225]

K. Spiekermann, J. Roesler, A. Emmendoerffer, et al., “Functional Features of Neutrophils Induced by G-CSF and GM-CSF Treatment: Differential Effects and Clinical Implications,” Leukemia 11, no. 4 (1997): 466-478.

[226]

Y. Li, S. Wu, Y. Zhao, et al., “Neutrophil Extracellular Traps Induced by Chemotherapy Inhibit Tumor Growth in Murine Models of Colorectal Cancer,” The Journal of Clinical Investigation 134, no. 5 (2024): e175031.

[227]

A. Mousset and J. Albrengues, “NETs Unleashed: Neutrophil Extracellular Traps Boost Chemotherapy Against Colorectal Cancer,” The Journal of Clinical Investigation 134, no. 5 (2024): e178344.

[228]

A. Ocana, C. Nieto-Jiménez, A. Pandiella, et al., “Neutrophils in Cancer: Prognostic Role and Therapeutic Strategies,” Molecular cancer 16, no. 1 (2017): 137.

[229]

F. Xun, W. Jiang, M. Sha, et al., “Neutrophil-to-lymphocyte Ratio in Colorectal Tissue Affects Prognosis in Patients With Colorectal Cancer,” Pathology 56, no. 5 (2024): 643-652.

[230]

W. Chua, K. A. Charles, V. E. Baracos, et al., “Neutrophil/Lymphocyte Ratio Predicts Chemotherapy Outcomes in Patients With Advanced Colorectal Cancer,” British Journal of Cancer 104, no. 8 (2011): 1288-1295.

[231]

W. Zhang, Y. Tan, Y. Li, et al., “Neutrophil to Lymphocyte Ratio as a Predictor for Immune-related Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis,” Frontiers In Immunology 14 (2023): 1234142.

[232]

S. Canè, R. M. Barouni, M. Fabbi, et al., “Neutralization of NET-associated human ARG1 Enhances Cancer Immunotherapy,” Science Translational Medicine 15, no. 687 (2023): eabq6221.

[233]

C. Thålin, S. Lundström, C. Seignez, et al., “Citrullinated Histone H3 as a Novel Prognostic Blood Marker in Patients With Advanced Cancer,” PLoS ONE 13, no. 1 (2018): e0191231.

[234]

B. Shang, H. Cui, R. Xie, et al., “Neutrophil Extracellular Traps Primed Intercellular Communication in Cancer Progression as a Promising Therapeutic Target,” Biomarker Research 11, no. 1 (2023): 24.

[235]

C. Hu, L. Long, J. Lou, et al., “CTC-neutrophil Interaction: A Key Driver and Therapeutic Target of Cancer Metastasis,” Biomedicine & Pharmacotherapy 180 (2024): 117474.

[236]

O. Marini, S. Costa, D. Bevilacqua, et al., “Mature CD10+ and Immature CD10- neutrophils Present in G-CSF-treated Donors Display Opposite Effects on T Cells,” Blood 129, no. 10 (2017): 1343-1356.

[237]

H. Que, Q. Fu, T. Lan, et al., “Tumor-associated Neutrophils and Neutrophil-targeted Cancer Therapies,” Biochimica Et Biophysica Acta Reviews On Cancer 1877, no. 5 (2022): 188762.

[238]

J. Leslie, J. B. G. Mackey, T. Jamieson, et al., “CXCR2 inhibition Enables NASH-HCC Immunotherapy,” Gut 71, no. 10 (2022): 2093-2106.

[239]

A. A. de Los Reyes and Y. Kim, “Optimal Regulation of Tumour-associated Neutrophils in Cancer Progression,” Royal Society Open Science 9, no. 2 (2022): 210705.

[240]

J. Wang, B. A. Tannous, M. C. Poznansky, et al., “CXCR4 antagonist AMD3100 (plerixafor): From an Impurity to a Therapeutic Agent,” Pharmacological Research 159 (2020): 105010.

[241]

G. Bao, Z. Wang, L. Liu, et al., “Targeting CXCR4/CXCL12 Axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 With CXCR4 Antagonist in Triple-negative Breast Cancer,” European Journal of Nuclear Medicine and Molecular Imaging 51, no. 9 (2024): 2744-2757.

[242]

V. Marin-Esteban, L. Molet, M. Laganà, et al., “CXCR4 Antagonist in HPV5-Associated Perianal Squamous-Cell Carcinoma,” New England Journal of Medicine 390, no. 14 (2024): 1339-1341.

[243]

J. Korbecki, M. Bosiacki, P. Kupnicka, et al., “CXCR4 as a Therapeutic Target in Acute Myeloid Leukemia,” Leukemia 38, no. 11 (2024): 2303-2317.

[244]

J. Gea-Banacloche, “Granulocyte Transfusions: A Concise Review for Practitioners,” Cytotherapy 19, no. 11 (2017): 1256-1269.

[245]

T. Yokomizo and T. Shimizu, “The Leukotriene B4 Receptors BLT1 and BLT2 as Potential Therapeutic Targets,” Immunological Reviews 317, no. 1 (2023): 30-41.

[246]

Y. Xin, S. Xiong, L. Zhou, et al., “Activation of Leukotriene B4 Receptor 1 Is a Prerequisite for Complement Receptor 3-mediated Antifungal Responses of Neutrophils,” Cellular & Molecular Immunology 21, no. 3 (2024): 245-259.

[247]

M. Joyal, R. D. Simard, W. Maharsy, et al., “Sialyl Lewisx Glycomimetics as E- and P-Selectin Antagonists Targeting Hyperinflammation,” Acs Medicinal Chemistry Letters 16, no. 1 (2025): 64-71.

[248]

G. Xiong, Z. Chen, Q. Liu, et al., “CD276 regulates the Immune Escape of Esophageal Squamous Cell Carcinoma Through CXCL1-CXCR2 Induced NETs,” Journal For Immunotherapy of Cancer 12, no. 5 (2024): e008662.

[249]

Z. Mou, Y. Chen, J. Hu, et al., “Icaritin Inhibits the Progression of Urothelial Cancer by Suppressing PADI2-mediated Neutrophil Infiltration and Neutrophil Extracellular Trap Formation,” Acta Pharm Sin B 14, no. 9 (2024): 3916-3930.

[250]

M. Yoshimoto, S. Kagawa, H. Kajioka, et al., “Dual Antiplatelet Therapy Inhibits Neutrophil Extracellular Traps to Reduce Liver Micrometastases of Intrahepatic Cholangiocarcinoma,” Cancer Letters 567 (2023): 216260.

[251]

C. Zhang, K. Cao, M. Yang, et al., “C5aR1 blockade Reshapes Immunosuppressive Tumor Microenvironment and Synergizes With Immune Checkpoint blockade Therapy in High-grade Serous Ovarian Cancer,” Oncoimmunology 12, no. 1 (2023): 2261242.

[252]

R. Stillie, S. M. Farooq, J. R. Gordon, et al., “The Functional Significance Behind Expressing Two IL-8 Receptor Types on PMN,” J Leukoc Biol 86, no. 3 (2009): 529-543.

[253]

J. Zhang, J. Gu, X. Wang, et al., “Engineering and Targeting Neutrophils for Cancer Therapy,” Advanced Materials 36, no. 19 (2024): e2310318.

[254]

Y. Cheng, F. Mo, Q. Li, et al., “Targeting CXCR2 Inhibits the Progression of Lung Cancer and Promotes Therapeutic Effect of Cisplatin,” Molecular Cancer 20, no. 1 (2021): 62.

[255]

A. F. Teixeira, P. Ten Dijke, and H.-J Zhu, “On-Target Anti-TGF-β Therapies Are Not Succeeding in Clinical Cancer Treatments: What Are Remaining Challenges?,” Frontiers In Cell and Developmental Biology 8 (2020): 605.

[256]

A. L. Marzo, D. R. Fitzpatrick, B. W. Robinson, et al., “Antisense Oligonucleotides Specific for Transforming Growth Factor beta2 Inhibit the Growth of Malignant Mesothelioma both in Vitro and in Vivo,” Cancer Research 57, no. 15 (1997): 3200-3207.

[257]

K. Sounbuli, N. Mironova, and L. Alekseeva, “Diverse Neutrophil Functions in Cancer and Promising Neutrophil-Based Cancer Therapies,” International Journal of Molecular Sciences 23, no. 24 (2022): 15827.

[258]

F. Qin, X. Liu, J. Chen, et al., “Anti-TGF-β Attenuates Tumor Growth via Polarization of Tumor Associated Neutrophils towards an Anti-tumor Phenotype in Colorectal Cancer,” Journal of Cancer 11, no. 9 (2020): 2580-2592.

[259]

L. Corrales, D. Ajona, S. Rafail, et al., “Anaphylatoxin C5a Creates a Favorable Microenvironment for Lung Cancer Progression,” Journal of Immunology 189, no. 9 (2012): 4674-4683.

[260]

Y. Song, J. Cao, Q. Zhang, et al., “Phase I Study of the Syk Inhibitor sovleplenib in Relapsed or Refractory Mature B-cell Tumors,” Haematologica 109, no. 7 (2024): 2165-2176.

[261]

M. A. Gouda, J. Shunyakova, A. Naing, et al., “A Phase I Study of TAK-659 and paclitaxel in Patients With Taxane-refractory Advanced Solid Tumors,” ESMO Open 9, no. 6 (2024): 103486.

[262]

Y. Hu, X. Liu, H. Zhou, et al., “Efficacy and Safety of sovleplenib (HMPL-523) in Adult Patients With Chronic Primary Immune Thrombocytopenia in China (ESLIM-01): A Randomised, Double-blind, Placebo-controlled, Phase 3 Study,” The Lancet Haematology 11, no. 8 (2024): e567-e579.

[263]

H.-H. Peter, H. D. Ochs, C. Cunningham-Rundles, et al., “Targeting FcRn for Immunomodulation: Benefits, Risks, and Practical Considerations,” Journal of Allergy and Clinical Immunology 146, no. 3 (2020): 479-491.

[264]

C. Yoo, M. M. Javle, H. Verdaguer Mata, et al., “Phase 2 Trial of bintrafusp alfa as Second-line Therapy for Patients With Locally Advanced/Metastatic Biliary Tract Cancers,” Hepatology 78, no. 3 (2023): 758-770.

[265]

N. Glodde, T. Bald, D. van den Boorn-Konijnenberg, et al., “Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy,” Immunity 47, no. 4 (2017): 789-802.

[266]

Y. Zhao, S. Rahmy, Z. Liu, et al., “Rational Targeting of Immunosuppressive Neutrophils in Cancer,” Pharmacology & Therapeutics 212 (2020): 107556.

[267]

H. L. Matlung, K. Szilagyi, N. A. Barclay, et al., “The CD47-SIRPα Signaling Axis as an Innate Immune Checkpoint in Cancer,” Immunological Reviews 276, no. 1 (2017): 145-164.

[268]

L. M. Behrens, T. K. van den Berg, and M. van Egmond, “Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils,” Cancers 14, no. 14 (2022): 3366.

[269]

A. Mehta, W. Harb, C. Xu, et al., “Lemzoparlimab, a Differentiated Anti-CD47 Antibody in Combination With Rituximab in Relapsed and Refractory Non- Hodgkin's Lymphoma: Initial Clinical Results,” Blood 138 (2021).

[270]

Y. Cheng, H. Li, Y. Deng, et al., “Cancer-associated Fibroblasts Induce PDL1+ Neutrophils Through the IL6-STAT3 Pathway That Foster Immune Suppression in Hepatocellular Carcinoma,” Cell Death & Disease 9, no. 4 (2018): 422.

[271]

M. A. Shah, T. Yoshino, N. C. Tebbutt, et al., “Napabucasin Plus FOLFIRI in Patients with Previously Treated Metastatic Colorectal Cancer: Results from the Open-Label, Randomized Phase III CanStem303C Study,” Clinical Colorectal Cancer 22, no. 1 (2023): 100-110.

[272]

A. M. Tsimberidou, D. J. Vining, S. P. Arora, et al., “Phase 1 Trial Evaluating TTI-101, a First-in-class, Orally Bioavailable, Small Molecule, Inhibitor of STAT3, in Patients With Advanced Solid Tumors,” Journal Of Clinical Oncology 41, no. 16 (2023).

[273]

T. Nishina, T. Fujita, N. Yoshizuka, et al., “Safety, Tolerability, Pharmacokinetics and Preliminary Antitumour Activity of an Antisense Oligonucleotide Targeting STAT3 (danvatirsen) as Monotherapy and in Combination With durvalumab in Japanese Patients With Advanced Solid Malignancies: A Phase 1 Study,” BMJ Open 12, no. 10 (2022): e055718.

[274]

B. Colom, J. V. Bodkin, M. Beyrau, et al., “Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration in Vivo,” Immunity 42, no. 6 (2015): 1075-1086.

[275]

A. Citro, A. Valle, E. Cantarelli, et al., “CXCR1/2 inhibition Blocks and Reverses Type 1 Diabetes in Mice,” Diabetes 64, no. 4 (2015): 1329-1340.

[276]

J. Nan, Y.-F. Xing, B. Hu, et al., “Endoplasmic Reticulum Stress Induced LOX-1+ CD15+ Polymorphonuclear Myeloid-derived Suppressor Cells in Hepatocellular Carcinoma,” Immunology 154, no. 1 (2018): 144-155.

[277]

T. R. J. Evans, B. Basu, R. Hubner, et al., “A Phase I/II Study of the CXCR2 Inhibitor, AZD5069, in Combination With durvalumab, in Patients (pts) With Advanced Hepatocellular Carcinoma (HCC),” Journal Of Clinical Oncology 41 (2023): TPS631-TPS631.

[278]

R. Esteban-Fabró, C. E. Willoughby, M. Piqué-Gili, et al., “Cabozantinib Enhances Anti-PD1 Activity and Elicits a Neutrophil-Based Immune Response in Hepatocellular Carcinoma,” Clinical Cancer Research: an Official Journal of the American Association For Cancer Research 28, no. 11 (2022): 2449-2460.

[279]

J. Xia, Z. Zhang, Y. Huang, et al., “Regulation of Neutrophil Extracellular Traps in Cancer,” International Journal of Cancer 154, no. 5 (2024): 773-785.

[280]

B. Knuckley, C. P. Causey, J. E. Jones, et al., “Substrate Specificity and Kinetic Studies of PADs 1, 3, and 4 Identify Potent and Selective Inhibitors of Protein Arginine Deiminase 3,” Biochemistry 49, no. 23 (2010): 4852-4863.

[281]

H. D. Lewis, J. Liddle, J. E. Coote, et al., “Inhibition of PAD4 Activity Is Sufficient to Disrupt Mouse and human NET Formation,” Nature Chemical Biology 11, no. 3 (2015): 189-191.

[282]

W. Jin, H. Yin, H. Li, et al., “Neutrophil Extracellular DNA Traps Promote Pancreatic Cancer Cells Migration and Invasion by Activating EGFR/ERK Pathway,” Journal of Cellular and Molecular Medicine 25, no. 12 (2021): 5443-5456.

[283]

H. Deng, C. Lin, L. Garcia-Gerique, et al., “A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression,” Cancer Research 82, no. 19 (2022): 3561-3572.

[284]

Z. Zhang, Q. Zhu, S. Wang, et al., “Epigallocatechin-3-gallate Inhibits the Formation of Neutrophil Extracellular Traps and Suppresses the Migration and Invasion of Colon Cancer Cells by Regulating STAT3/CXCL8 Pathway,” Molecular and Cellular Biochemistry 478, no. 4 (2023): 887-898.

[285]

R. Suri, “The Use of human Deoxyribonuclease (rhDNase) in the Management of Cystic Fibrosis,” Biodrugs 19, no. 3 (2005): 135-144.

[286]

Y. Xia, J. He, H. Zhang, et al., “AAV-mediated Gene Transfer of DNase I in the Liver of Mice With Colorectal Cancer Reduces Liver Metastasis and Restores Local Innate and Adaptive Immune Response,” Mol Oncol 14, no. 11 (2020): 2920-2935.

[287]

M. Nie, L. Yang, X. Bi, et al., “Neutrophil Extracellular Traps Induced by IL8 Promote Diffuse Large B-cell Lymphoma Progression via the TLR9 Signaling,” Clinical Cancer Research: an Official Journal of the American Association For Cancer Research 25, no. 6 (2019): 1867-1879.

[288]

R. F. Rayes, J. G. Mouhanna, I. Nicolau, et al., “Primary Tumors Induce Neutrophil Extracellular Traps With Targetable Metastasis Promoting Effects,” JCI Insight 5, no. 16 (2019): e128008.

[289]

F. H. Al-Awadhi, P. VJ, and H. Luesch, “Structural Diversity and Anticancer Activity of Marine-Derived Elastase Inhibitors: Key Features and Mechanisms Mediating the Antimetastatic Effects in Invasive Breast Cancer,” Chembiochem 19, no. 8 (2018): 815-825.

[290]

Y. Yang, L. Ma, Y. Xu, et al., “Enalapril Overcomes Chemoresistance and Potentiates Antitumor Efficacy of 5-FU in Colorectal Cancer by Suppressing Proliferation, Angiogenesis, and NF-κB/STAT3-regulated Proteins,” Cell Death & Disease 11, no. 6 (2020): 477.

[291]

M. A. Subhan and V. P Torchilin, “Neutrophils as an Emerging Therapeutic Target and Tool for Cancer Therapy,” Life Sciences 285 (2021): 119952.

[292]

D. Chu, X. Dong, X. Shi, et al., “Neutrophil-Based Drug Delivery Systems,” Advanced Materials (Deerfield Beach, Fla) 30, no. 22 (2018): e1706245.

[293]

C. Ju, Y. Wen, L. Zhang, et al., “Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals With Radiotherapy for Gastric Cancer,” Small 15, no. 5 (2019): e1804191.

[294]

O. M. Elsharkasy, J. Z. Nordin, D. W. Hagey, et al., “Extracellular Vesicles as Drug Delivery Systems: Why and How?,” Advanced Drug Delivery Reviews 159 (2020): 332-343.

[295]

S. B. Coffelt, K. Kersten, C. W. Doornebal, et al., “IL-17-producing Γδ T Cells and Neutrophils Conspire to Promote Breast Cancer Metastasis,” Nature 522, no. 7556 (2015): 345-348.

[296]

J. Wang, W. Tang, M. Yang, et al., “Inflammatory Tumor Microenvironment Responsive Neutrophil Exosomes-based Drug Delivery System for Targeted Glioma Therapy,” Biomaterials 273 (2021): 120784.

[297]

Z. Wang, C. Chen, C. Shi, et al., “Cell Membrane Derived Liposomes Loaded With DNase I Target Neutrophil Extracellular Traps Which Inhibits Colorectal Cancer Liver Metastases,” J Control Release 357 (2023): 620-629.

[298]

J. Chen, S. Hou, Q. Liang, et al., “Localized Degradation of Neutrophil Extracellular Traps by Photoregulated Enzyme Delivery for Cancer Immunotherapy and Metastasis Suppression,” ACS Nano 16, no. 2 (2022): 2585-2597.

[299]

H. Liang, Y. Du, C. Zhu, et al., “Nanoparticulate Cationic Poly(amino acid)s Block Cancer Metastases by Destructing Neutrophil Extracellular Traps,” ACS Nano 17, no. 3 (2023): 2868-2880.

[300]

Y. Chang, R. Syahirah, X. Wang, et al., “Engineering Chimeric Antigen Receptor Neutrophils From human Pluripotent Stem Cells for Targeted Cancer Immunotherapy,” Cell Reports 40, no. 3 (2022): 111128.

[301]

D. H. McDermott, D. Velez, E. Cho, et al., “A Phase III Randomized Crossover Trial of plerixafor versus G-CSF for Treatment of WHIM Syndrome,” The Journal of Clinical Investigation 133, no. 19 (2023): e164918.

[302]

M. A. Cruz, D. Bohinc, E. A. Andraska, et al., “Nanomedicine Platform for Targeting Activated Neutrophils and Neutrophil-platelet Complexes Using an α1-antitrypsin-derived Peptide Motif,” Nature Nanotechnology 17, no. 9 (2022): 1004-1014.

[303]

A. O. Yam and T. Chtanova, “Imaging the Neutrophil: Intravital Microscopy Provides a Dynamic View of Neutrophil Functions in Host Immunity,” Cellular Immunology 350 (2020): 103898.

[304]

S. Pulikkot, M. Zhao, and Z. Fan, “Real-Time Measurement of the Mitochondrial Bioenergetic Profile of Neutrophils,” Journal of visualized experiments: JoVE 196 (2023): 10.3791/64971.

[305]

F. S. Grudzinska, A. Jasper, E. Sapey, et al., “Real-time Assessment of Neutrophil Metabolism and Oxidative Burst Using Extracellular Flux Analysis,” Frontiers In Immunology 14 (2023): 1083072.

[306]

Y. Fan, Y. Teng, F. Loison, et al., “Targeting Multiple Cell Death Pathways Extends the Shelf Life and Preserves the Function of human and Mouse Neutrophils for Transfusion,” Science Translational Medicine 13, no. 604 (2021): eabb1069.

[307]

C. Li, N. W. Hendrikse, M. Mai, et al., “Microliter Whole Blood Neutrophil Assay Preserving Physiological Lifespan and Functional Heterogeneity,” Small Methods 8, no. 9 (2024): e2400373.

[308]

Y. Zhang, L. Guoqiang, M. Sun, et al., “Targeting and Exploitation of Tumor-associated Neutrophils to Enhance Immunotherapy and Drug Delivery for Cancer Treatment,” Cancer Biology & Medicine 17, no. 1 (2020): 32-43.

[309]

Z. J. Brown, B. Heinrich, and T. F Greten, “Mouse Models of Hepatocellular Carcinoma: An Overview and Highlights for Immunotherapy Research,” Nature Reviews Gastroenterology & Hepatology 15, no. 9 (2018): 536-554.

[310]

A. J. Kwok, A. Allcock, R. C. Ferreira, et al., “Neutrophils and Emergency Granulopoiesis Drive Immune Suppression and an Extreme Response Endotype During Sepsis,” Nature Immunology 24, no. 5 (2023): 767-779.

[311]

M. Lenz, T. Maiberger, L. Armbrust, et al., “cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates-A Pilot Study,” Cells 11, no. 2 (2022): 192.

[312]

L. Stiel, C. Mayeur-Rousse, J. Helms, et al., “First Visualization of Circulating Neutrophil Extracellular Traps Using Cell Fluorescence During human Septic Shock-induced Disseminated Intravascular Coagulation,” Thrombosis Research 183 (2019): 153-158.

[313]

H. Zhang, Y. Wang, M. Qu, et al., “Neutrophil, Neutrophil Extracellular Traps and Endothelial Cell Dysfunction in Sepsis,” Clinical and Translational Medicine 13, no. 1 (2023): e1170.

[314]

E. Maneta, E. Aivalioti, S. Tual-Chalot, et al., “Endothelial Dysfunction and Immunothrombosis in Sepsis,” Frontiers In Immunology 14 (2023): 1144229.

[315]

Z. Li, M. K. Delaney, and K. A. O'Brien, “Signaling During Platelet Adhesion and Activation,” Arteriosclerosis, Thrombosis, and Vascular Biology 30, no. 12 (2010): 2341-2349.

[316]

Z. Chen, H. Zhang, M. Qu, et al., “Review: The Emerging Role of Neutrophil Extracellular Traps in Sepsis and Sepsis-Associated Thrombosis,” Frontiers in Cellular and Infection Microbiology 11 (2021): 653228.

[317]

B. D. Kevadiya, J. Machhi, J. Herskovitz, et al., “Diagnostics for SARS-CoV-2 Infections,” Nature Materials 20, no. 5 (2021): 593-605.

[318]

M. Liao, Y. Liu, J. Yuan, et al., “Single-cell Landscape of Bronchoalveolar Immune Cells in Patients With COVID-19,” Nature Medicine 26, no. 6 (2020): 842-844.

[319]

A. Bonaventura, A. Vecchié, L. Dagna, et al., “Endothelial Dysfunction and Immunothrombosis as Key Pathogenic Mechanisms in COVID-19,” Nature Reviews Immunology 21, no. 5 (2021): 319-329.

[320]

R. Zhang, C. Sun, Y. Han, et al., “Neutrophil Autophagy and NETosis in COVID-19: Perspectives,” Autophagy 19, no. 3 (2023): 758-767.

[321]

E. A. Middleton, X.-Y. He, F. Denorme, et al., “Neutrophil Extracellular Traps Contribute to Immunothrombosis in COVID-19 Acute respiratory Distress Syndrome,” Blood 136, no. 10 (2020): 1169-1179.

[322]

R. Channappanavar and S. Perlman, “Pathogenic human Coronavirus Infections: Causes and Consequences of Cytokine Storm and Immunopathology,” Seminars in immunopathology 39, no. 5 (2017): 529-539.

[323]

B. G. Chousterman, F. K. Swirski, and G. F Weber, “Cytokine Storm and Sepsis Disease Pathogenesis,” Seminars in immunopathology 39, no. 5 (2017): 517-528.

[324]

M. C. Cesta, M. Zippoli, C. Marsiglia, et al., “Neutrophil Activation and Neutrophil Extracellular Traps (NETs) in COVID-19 ARDS and Immunothrombosis,” European Journal of Immunology 53, no. 1 (2023): e2250010.

[325]

P. Skendros, A. Mitsios, A. Chrysanthopoulou, et al., “Complement and Tissue Factor-enriched Neutrophil Extracellular Traps Are Key Drivers in COVID-19 Immunothrombosis,” The Journal of Clinical Investigation 130, no. 11 (2020): 6151-6157.

[326]

J. Zhao, J. Ma, Y. Deng, et al., “A Missense Variant in NCF1 Is Associated With Susceptibility to Multiple Autoimmune Diseases,” Nature Genetics 49, no. 3 (2017): 433-437.

[327]

F. Apel, A. Zychlinsky, and E. F Kenny, “The Role of Neutrophil Extracellular Traps in Rheumatic Diseases,” Nat Rev Rheumatol 14, no. 8 (2018): 467-475.

[328]

G. Wigerblad and M. J Kaplan, “Neutrophil Extracellular Traps in Systemic Autoimmune and Autoinflammatory Diseases,” Nature Reviews Immunology 23, no. 5 (2023): 274-288.

[329]

S. Ma, W. Jiang, X. Zhang, et al., “Insights Into the Pathogenic Role of Neutrophils in Systemic Lupus Erythematosus,” Current Opinion in Rheumatology 35, no. 2 (2023): 82-88.

[330]

A. Hoi, T. Igel, C. C. Mok, et al., “Systemic lupus erythematosus,” Lancet 403, no. 10441 (2024): 2326-2338.

[331]

C. Carmona-Rivera and M. J Kaplan, “Low-density Granulocytes in Systemic Autoimmunity and Autoinflammation,” Immunological Reviews 314, no. 1 (2023): 313-325.

[332]

P. Li, M. Jiang, K. Li, et al., “Glutathione Peroxidase 4-regulated Neutrophil Ferroptosis Induces Systemic Autoimmunity,” Nature Immunology 22, no. 9 (2021): 1107-1117.

[333]

W. Qiu, T. Yu, and G.-M Deng, “The Role of Organ-deposited IgG in the Pathogenesis of Multi-organ and Tissue Damage in Systemic Lupus Erythematosus,” Frontiers In Immunology 13 (2022): 924766.

[334]

S. Rahman, D. Sagar, R. N. Hanna, et al., “Low-density Granulocytes Activate T Cells and Demonstrate a Non-suppressive Role in Systemic Lupus Erythematosus,” Annals of the Rheumatic Diseases 78, no. 7 (2019): 957-966.

[335]

S. Caielli, S. Athale, B. Domic, et al., “Oxidized Mitochondrial Nucleoids Released by Neutrophils Drive Type I Interferon Production in human Lupus,” The Journal of Experimental Medicine 213, no. 5 (2016): 697-713.

[336]

J. M. Kahlenberg, C. Carmona-Rivera, C. K. Smith, et al., “Neutrophil Extracellular Trap-associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages,” Journal of Immunology 190, no. 3 (2013): 1217-1226.

[337]

Q. Liu, W. Zhu, X. Wen, et al., “The Role of Platelet-Neutrophil Interactions in Driving Autoimmune Diseases,” Immunology 175, no. 1 (2025): 1-15.

[338]

C. Carmona-Rivera, W. Zhao, S. Yalavarthi, et al., “Neutrophil Extracellular Traps Induce Endothelial Dysfunction in Systemic Lupus Erythematosus Through the Activation of Matrix Metalloproteinase-2,” Annals of the Rheumatic Diseases 74, no. 7 (2015): 1417-1424.

[339]

W. G. Ambler and M. J Kaplan, “Vascular Damage in Systemic Lupus erythematosus,” Nature Reviews Nephrology 20, no. 4 (2024): 251-265.

[340]

C. K. Smith, A. Vivekanandan-Giri, C. Tang, et al., “Neutrophil Extracellular Trap-derived Enzymes Oxidize High-density Lipoprotein: An Additional Proatherogenic Mechanism in Systemic Lupus Erythematosus,” Arthritis Rheumatol 66, no. 9 (2014): 2532-2544.

[341]

S. Skopelja-Gardner, J. Tai, X. Sun, et al., “Acute Skin Exposure to Ultraviolet Light Triggers Neutrophil-mediated Kidney Inflammation,” Proceedings of the National Academy of Sciences of the United States of America 118, no. 3 (2021): e2019097118.

[342]

A. Di Matteo, J. M. Bathon, and P. Emery, “Rheumatoid Arthritis,” Lancet 402, no. 10416 (2023): 2019-2033.

[343]

G. Steiner and R. E. M Toes, “Autoantibodies in Rheumatoid Arthritis—rheumatoid Factor, Anticitrullinated Protein Antibodies and Beyond,” Current Opinion in Rheumatology 36, no. 3 (2024): 217-224.

[344]

E. Corsiero, F. Pratesi, E. Prediletto, et al., “NETosis as Source of Autoantigens in Rheumatoid Arthritis,” Frontiers In Immunology 7 (2016): 485.

[345]

L. J. O'Neil, A. Barrera-Vargas, D. Sandoval-Heglund, et al., “Neutrophil-mediated Carbamylation Promotes Articular Damage in Rheumatoid Arthritis,” Science Advances 6, no. 44 (2020): eabd2688.

[346]

R. Khandpur, C. Carmona-Rivera, A. Vivekanandan-Giri, et al., “NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis,” Science Translational Medicine 5, no. 178 (2013): 178ra140.

[347]

C. L. Too, S. Murad, J. S. Dhaliwal, et al., “Polymorphisms in Peptidylarginine Deiminase Associate With Rheumatoid Arthritis in Diverse Asian Populations: Evidence From MyEIRA Study and Meta-analysis,” Arthritis Research & Therapy 14, no. 6 (2012): R250.

[348]

M. Sadeghi, S. Dehnavi, T. Jamialahmadi, et al., “Neutrophil Extracellular Trap: A Key Player in the Pathogenesis of Autoimmune Diseases,” International Immunopharmacology 116 (2023): 109843.

[349]

C. Carmona-Rivera, P. M. Carlucci, R. R. Goel, et al., “Neutrophil Extracellular Traps Mediate Articular Cartilage Damage and Enhance Cartilage Component Immunogenicity in Rheumatoid Arthritis,” JCI Insight 5, no. 13 (2020): e139388.

[350]

Z. Wang, Y. Jiao, W. Diao, et al., “Neutrophils: A Central Point of Interaction between Immune Cells and Nonimmune Cells in Rheumatoid Arthritis,” Clinical Reviews in Allergy & Immunology 68, no. 1 (2025): 34.

[351]

H. Katayama, “Rheumatoid Arthritis: Development After the Emergence of a Chemokine for Neutrophils in the Synovium,” BioEssays 43, no. 10 (2021): e2100119.

[352]

H. Ye, Q. Yang, H. Guo, et al., “Internalisation of Neutrophils Extracellular Traps by Macrophages Aggravate Rheumatoid Arthritis via Rab5a,” RMD Open 10, no. 1 (2024): fcaa132.

[353]

L. Donis-Maturano, L. E. Sánchez-Torres, A. Cerbulo-Vázquez, et al., “Prolonged Exposure to Neutrophil Extracellular Traps Can Induce Mitochondrial Damage in Macrophages and Dendritic Cells,” Springerplus 4 (2015): 161.

[354]

J. Chen, Y. Cao, J. Xiao, et al., “The Emerging Role of Neutrophil Extracellular Traps in the Progression of Rheumatoid Arthritis,” Frontiers In Immunology 15 (2024): 1438272.

[355]

M. Ayub, J. HK, and J.-S Bae, “The Blood Cerebrospinal Fluid Barrier Orchestrates Immunosurveillance, Immunoprotection, and Immunopathology in the central Nervous System,” BMB Reports 54, no. 4 (2021): 196-202.

[356]

B. Santos-Lima, E. C. Pietronigro, E. Terrabuio, et al., “The Role of Neutrophils in the Dysfunction of central Nervous System Barriers,” Frontiers in aging neuroscience 14 (2022): 965169.

[357]

M.-L. Chou, A. O. Babamale, T. L. Walker, et al., “Blood-brain Crosstalk: The Roles of Neutrophils, Platelets, and Neutrophil Extracellular Traps in Neuropathologies,” Trends in Neuroscience (Tins) 46, no. 9 (2023): 764-779.

[358]

P. Scheltens, B. De Strooper, M. Kivipelto, et al., “Alzheimer's Disease,” Lancet 397, no. 10284 (2021): 1577-1590.

[359]

L. Song, Y. T. Yang, Q. Guo, et al., “Cellular Transcriptional Alterations of Peripheral Blood in Alzheimer's Disease,” BMC Medicine [Electronic Resource] 20, no. 1 (2022): 266.

[360]

L. C. D. Smyth, H. C. Murray, M. Hill, et al., “Neutrophil-vascular Interactions Drive Myeloperoxidase Accumulation in the Brain in Alzheimer's disease,” Acta Neuropathol Commun 10, no. 1 (2022): 38.

[361]

E. C. Pietronigro, V. Della Bianca, and E. Zenaro, “NETosis in Alzheimer's Disease,” Frontiers In Immunology 8 (2017): 211.

[362]

C. Allen, P. Thornton, A. Denes, et al., “Neutrophil Cerebrovascular Transmigration Triggers Rapid Neurotoxicity Through Release of Proteases Associated With Decondensed DNA,” Journal of Immunology 189, no. 1 (2012): 381-392.

[363]

M. R. DiStasi and K. Ley, “Opening the Flood-gates: How Neutrophil-endothelial Interactions Regulate Permeability,” Trends in Immunology 30, no. 11 (2009): 547-556.

[364]

Q. Zhang, G. Yang, Y. Luo, et al., “Neuroinflammation in Alzheimer's Disease: Insights From Peripheral Immune Cells,” Immun Ageing 21, no. 1 (2024): 38.

[365]

I. Salken, J. J. Provencio, and A. P Coulibaly, “A Potential Therapeutic Target: The Role of Neutrophils in the central Nervous System,” Brain Behav Immun Health 33 (2023): 100688.

[366]

E. Zenaro, E. Pietronigro, V. Della Bianca, et al., “Neutrophils Promote Alzheimer's Disease-Like Pathology and Cognitive Decline via LFA-1 Integrin,” Nature Medicine 21, no. 8 (2015): 880-886.

[367]

D. F Stroncek, “Neutrophil-specific Antigen HNA-2a, NB1 Glycoprotein, and CD177,” Current Opinion in Hematology 14, no. 6 (2007): 688-693.

[368]

E. P. C. Azevedo, A. B. Guimarães-Costa, G. S. Torezani, et al., “Amyloid Fibrils Trigger the Release of Neutrophil Extracellular Traps (NETs), Causing Fibril Fragmentation by NET-associated Elastase,” Journal of Biological Chemistry 287, no. 44 (2012): 37206-37218.

[369]

M. T. Heneka, M. J. Carson, and J. El Khoury, “Neuroinflammation in Alzheimer's Disease,” Lancet Neurology 14, no. 4 (2015): 388-405.

[370]

A. García-Culebras, M. I. Cuartero, C. Peña-Martínez, et al., “Myeloid Cells in Vascular Dementia and Alzheimer's Disease: Possible Therapeutic Targets?,” British Journal of Pharmacology 181, no. 6 (2024): 777-798.

[371]

M. L. Aries and T. Hensley-McBain, “Neutrophils as a Potential Therapeutic Target in Alzheimer's Disease,” Frontiers In Immunology 14 (2023): 1123149.

[372]

K. Kulcsarova, M. Skorvanek, R. B. Postuma, et al., “Defining Parkinson's Disease: Past and Future,” J Parkinsons Dis 14, no. s2 (2024): S257-S271.

[373]

B. R. Bloem, M. S. Okun, and C. Klein, “Parkinson's Disease,” Lancet 397, no. 10291 (2021): 2284-2303.

[374]

S. A. Ferreira and M. Romero-Ramos, “Microglia Response during Parkinson's Disease: Alpha-Synuclein Intervention,” Front Cell Neurosci 12 (2018): 247.

[375]

M. G. Tansey, R. L. Wallings, M. C. Houser, et al., “Inflammation and Immune Dysfunction in Parkinson disease,” Nature Reviews Immunology 22, no. 11 (2022): 657-673.

[376]

G. P. Williams, A. M. Schonhoff, A. Sette, et al., “Central and Peripheral Inflammation: Connecting the Immune Responses of Parkinson's Disease,” J Parkinsons Dis 12, no. s1 (2022): S129-S136.

[377]

R. Kim, N. Kang, K. Byun, et al., “Prognostic Significance of Peripheral Neutrophils and Lymphocytes in Early Untreated Parkinson's Disease: An 8-year Follow-up Study,” Journal of Neurology, Neurosurgery, and Psychiatry 94, no. 12 (2023): 1040-1046.

[378]

R. Lin, G. Cai, Y. Chen, et al., “Association of Glymphatic System Function With Peripheral Inflammation and Motor Symptoms in Parkinson's Disease,” NPJ Parkinsons Dis 11, no. 1 (2025): 62.

[379]

J. Tian, S.-B. Dai, S.-S. Jiang, et al., “Specific Immune Status in Parkinson's Disease at Different Ages of Onset,” NPJ Parkinsons Dis 8, no. 1 (2022): 5.

[380]

D. W. Craig, E. Hutchins, I. Violich, et al., “RNA Sequencing of Whole Blood Reveals Early Alterations in Immune Cells and Gene Expression in Parkinson's Disease,” Nat Aging 1, no. 8 (2021): 734-747.

[381]

Y. Yuan, H. Li, K. Sreeram, et al., “Single Molecule Array Measures of LRRK2 Kinase Activity in Serum Link Parkinson's Disease Severity to Peripheral Inflammation,” Mol Neurodegener 19, no. 1 (2024): 47.

[382]

D. A. Cook, G. T. Kannarkat, A. F. Cintron, et al., “LRRK2 levels in Immune Cells Are Increased in Parkinson's Disease,” NPJ Parkinsons Dis 3 (2017): 11.

[383]

N. Dzamko, F. Inesta-Vaquera, J. Zhang, et al., “The IkappaB Kinase family Phosphorylates the Parkinson's Disease Kinase LRRK2 at Ser935 and Ser910 During Toll-Like Receptor Signaling,” PLoS ONE 7, no. 6 (2012): e39132.

[384]

A. Kouli, C. B. Horne, and W-G. CH, “Toll-Like Receptors and Their Therapeutic Potential in Parkinson's Disease and α-synucleinopathies,” Brain, Behavior, and Immunity 81 (2019): 41-51.

[385]

X. Chen, Y. Hu, Z. Cao, et al., “Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis,” Frontiers In Immunology 9 (2018): 2122.

[386]

Y. Huang, H. Liu, J. Hu, et al., “Significant Difference of Immune Cell Fractions and Their Correlations with Differential Expression Genes in Parkinson's Disease,” Frontiers in aging neuroscience 13 (2021): 686066.

[387]

E.-K. Tan, Y.-X. Chao, A. West, et al., “Parkinson Disease and the Immune System—associations, Mechanisms and Therapeutics,” Nature reviews Neurology 16, no. 6 (2020): 303-318.

[388]

T. Shen, G. Cui, H. Chen, et al., “TREM-1 Mediates Interaction Between Substantia nigra Microglia and Peripheral Neutrophils,” Neural Regen Res 19, no. 6 (2024): 1375-1384.

[389]

C. Tecchio, A. Micheletti, and M. A Cassatella, “Neutrophil-derived Cytokines: Facts Beyond Expression,” Frontiers In Immunology 5 (2014): 508.

[390]

M. G. Tansey and M. Romero-Ramos, “Immune System Responses in Parkinson's disease: Early and Dynamic,” European Journal of Neuroscience 49, no. 3 (2019): 364-383.

[391]

L. Muñoz-Delgado, M. Á. Labrador-Espinosa, D. Macías-García, et al., “Peripheral Inflammation Is Associated With Dopaminergic Degeneration in Parkinson's Disease,” Movement Disorders 38, no. 5 (2023): 755-763.

[392]

E. Ahmad, S. Lim, R. Lamptey, et al., “Type 2 Diabetes,” Lancet 400, no. 10365 (2022): 1803-1820.

[393]

M. K. Ali, J. Pearson-Stuttard, E. Selvin, et al., “Interpreting Global Trends in Type 2 Diabetes Complications and Mortality,” Diabetologia 65, no. 1 (2022): 3-13.

[394]

P. Y. Thimmappa, S. Vasishta, K. Ganesh, et al., “Neutrophil (dys)Function due to Altered Immuno-metabolic Axis in Type 2 Diabetes: Implications in Combating Infections,” Human Cell 36, no. 4 (2023): 1265-1282.

[395]

J. L. Floyd, R. Prasad, M. D. Dupont, et al., “Intestinal Neutrophil Extracellular Traps Promote Gut Barrier Damage Exacerbating Endotoxaemia, Systemic Inflammation and Progression of Diabetic Retinopathy in Type 2 Diabetes,” Diabetologia 68, no. 4 (2025): 866-889.

[396]

A. Giovenzana, D. Carnovale, B. Phillips, et al., “Neutrophils and Their Role in the Aetiopathogenesis of Type 1 and Type 2 Diabetes,” Diabetes Metabolism Research and Reviews 38, no. 1 (2022): e3483.

[397]

A. Farhan, G. Hassan, S. H. L. Ali, et al., “Spontaneous NETosis in Diabetes: A Role of Hyperglycemia Mediated ROS and Autophagy,” Front Med (Lausanne) 10 (2023): 1076690.

[398]

S. Yang, Z. Gu, C. Lu, et al., “Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients With Diabetic Foot Ulcers Treated in a Multidisciplinary Setting,” Adv Wound Care (New Rochelle) 9, no. 1 (2020): 16-27.

[399]

G. Kolumam, X. Wu, W. P. Lee, et al., “IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice,” PLoS ONE 12, no. 1 (2017): e0170639.

[400]

B. L. Dumont, P.-E. Neagoe, E. Charles, et al., “Low-Density Neutrophils Contribute to Subclinical Inflammation in Patients With Type 2 Diabetes,” International Journal of Molecular Sciences 25, no. 3 (2024): 1674.

[401]

D. Tsilingiris, A.-M. Natsi, E. Gavriilidis, et al., “Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes Through Neutrophil Extracellular Traps-Fibroblast Crosstalk,” European Journal of Immunology 55, no. 4 (2025): e202451664.

[402]

T. T. Nguyen, D. Ding, W. R. Wolter, et al., “Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing,” Journal of Medicinal Chemistry 61, no. 19 (2018): 8825-8837.

[403]

L. Rong, J. Zou, W. Ran, et al., “Advancements in the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD),” Front Endocrinol (Lausanne) 13 (2022): 1087260.

[404]

L. Hammerich and F. Tacke, “Hepatic Inflammatory Responses in Liver Fibrosis,” Nature Reviews Gastroenterology & Hepatology 20, no. 10 (2023): 633-646.

[405]

J. M. Llovet, C. E. Willoughby, A. G. Singal, et al., “Nonalcoholic Steatohepatitis-related Hepatocellular Carcinoma: Pathogenesis and Treatment,” Nature Reviews Gastroenterology & Hepatology 20, no. 8 (2023): 487-503.

[406]

J. Fang, C.-H. Yu, X.-J. Li, et al., “Gut Dysbiosis in Nonalcoholic Fatty Liver Disease: Pathogenesis, Diagnosis, and Therapeutic Implications,” Frontiers in Cellular and Infection Microbiology 12 (2022): 997018.

[407]

H. Wang, W. Mehal, L. E. Nagy, et al., “Immunological Mechanisms and Therapeutic Targets of Fatty Liver Diseases,” Cellular & Molecular Immunology 18, no. 1 (2021): 73-91.

[408]

S. Hwang, Y. He, X. Xiang, et al., “Interleukin-22 Ameliorates Neutrophil-Driven Nonalcoholic Steatohepatitis through Multiple Targets,” Hepatology 72, no. 2 (2020): 412-429.

[409]

P. Fa, B. G. Ke, A. Dupre, et al., “The Implication of Neutrophil Extracellular Traps in Nonalcoholic Fatty Liver Disease,” Frontiers In Immunology 14 (2023): 1292679.

[410]

R. Jiang, Z. Tan, L. Deng, et al., “Interleukin-22 Promotes human Hepatocellular Carcinoma by Activation of STAT3,” Hepatology 54, no. 3 (2011): 900-909.

[411]

G. Xu, Y.-M. Wang, M.-M. Ying, et al., “Serum Lipocalin-2 Is a Potential Biomarker for the Clinical Diagnosis of Nonalcoholic Steatohepatitis,” Clin Mol Hepatol 27, no. 2 (2021): 329-345.

[412]

D. Ye, K. Yang, S. Zang, et al., “Lipocalin-2 Mediates Non-alcoholic Steatohepatitis by Promoting Neutrophil-macrophage Crosstalk via the Induction of CXCR2,” Journal of Hepatology 65, no. 5 (2016): 988-997.

[413]

L. Yang, Y. Hao, J. Boeckmans, et al., “Immune Cells and Their Derived microRNA-enriched Extracellular Vesicles in Nonalcoholic Fatty Liver Diseases: Novel Therapeutic Targets,” Pharmacology & Therapeutics 243 (2023): 108353.

[414]

H. Gao, Z. Jin, G. Bandyopadhyay, et al., “MiR-690 Treatment Causes Decreased Fibrosis and Steatosis and Restores Specific Kupffer Cell Functions in NASH,” Cell metabolism 34, no. 7 (2022): 978-990.

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