{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:30:32Z","timestamp":1789659032204,"version":"4.0.1"},"reference-count":137,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital, Kaohsiung, Taiwan","award":["CMRPG8N0241"],"award-info":[{"award-number":["CMRPG8N0241"]}],"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Chang Gung Memorial Hospital, Kaohsiung, Taiwan","award":["CMRPG8N0242"],"award-info":[{"award-number":["CMRPG8N0242"]}],"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"crossref"}]},{"award":["CMRPG8N0241"],"award-info":[{"award-number":["CMRPG8N0241"]}],"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CMRPG8N0242"],"award-info":[{"award-number":["CMRPG8N0242"]}],"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neutrophil extracellular trap formation (NETosis) has emerged as a pivotal regulator of the tumor immune microenvironment and a key determinant of response to cancer immunotherapy. NETs\u2014web-like chromatin fibers decorated with histones, citrullinated histone H3, myeloperoxidase, neutrophil elastase, and matrix metalloproteinase-9\u2014are induced by tumor-derived signals through classical lytic, vital non-lytic, and gasdermin D-dependent pathways, and exert context-dependent, predominantly pro-tumorigenic effects. Within the tumor microenvironment, NETs remodel the stroma, suppress CD8+ T-cell, natural killer-cell, and dendritic-cell function, promote regulatory T-cell and M2 macrophage polarization, and physically shield tumor cells from cytotoxic attack. By carrying programmed death-ligand 1 and driving T-cell exhaustion and immune exclusion, NETs compromise the efficacy of immune checkpoint inhibitors (ICIs) targeting PD-1\/PD-L1, CTLA-4, and next-generation checkpoints, as well as adoptive cell therapies. This review synthesizes the molecular mechanisms of NETosis, its multifaceted immunomodulatory roles, and emerging NET-derived biomarkers\u2014including MPO-DNA and citrullinated histone H3-DNA complexes\u2014that may predict immunotherapy response and toxicity. We further appraise therapeutic strategies, including PAD4 inhibitors, DNase I, CXCR2 antagonists, and nanoparticle-based platforms, and underscore the need for standardized NET quantification, careful preservation of host defense, and biomarker-guided clinical trials to translate NET modulation into durable improvements in immunotherapy outcomes.<\/jats:p>","DOI":"10.3390\/ijms27188278","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"8278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3310-7678","authenticated-orcid":false,"given":"Chung-Wen","family":"Kuo","sequence":"first","affiliation":[{"name":"Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-1718","authenticated-orcid":false,"given":"Hsin-Ying Clair","family":"Chiou","sequence":"additional","affiliation":[{"name":"Genomic & Proteomic Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Applied Chemistry, National Chi Nan University, Nantou 54561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-2285","authenticated-orcid":false,"given":"Shih-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-2941","authenticated-orcid":false,"given":"Chia-Che","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1289-473X","authenticated-orcid":false,"given":"Yu-Li","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Genomic & Proteomic Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Doctoral Program of Clinical and Experimental Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan"},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan"},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1182\/blood-2013-04-457671","article-title":"NETosis: How vital is it?","volume":"122","author":"Yipp","year":"2013","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1007\/s00018-016-2195-0","article-title":"Matters of life and death. How neutrophils die or survive along NET release and is \u201cNETosis\u201d = necroptosis?","volume":"73","author":"Desai","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, Y., Du, C., Zhang, Y., and Zhu, L. (2024). Composition and Function of Neutrophil Extracellular Traps. Biomolecules, 14.","DOI":"10.3390\/biom14040416"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eabj2101","DOI":"10.1126\/sciadv.abj2101","article-title":"Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens","volume":"7","author":"Monteith","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bryzek, D., Ciaston, I., Dobosz, E., Gasiorek, A., Makarska, A., Sarna, M., Eick, S., Puklo, M., Lech, M., and Potempa, B. (2019). Triggering NETosis via protease-activated receptor (PAR)-2 signaling as a mechanism of hijacking neutrophils function for pathogen benefits. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007773"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/cdd.2011.1","article-title":"Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality","volume":"18","author":"Remijsen","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schoen, J., Euler, M., Schauer, C., Schett, G., Herrmann, M., Knopf, J., and Yaykasli, K.O. (2022). Neutrophils\u2019 Extracellular Trap Mechanisms: From Physiology to Pathology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112855"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e162","DOI":"10.1002\/mco2.162","article-title":"Molecular mechanisms and therapeutic target of NETosis in diseases","volume":"3","author":"Huang","year":"2022","journal-title":"MedComm"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-024-01933-x","article-title":"Neutrophil extracellular traps in homeostasis and disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lao, Y., Shen, D., Zhang, W., He, R., and Jiang, M. (2022). Immune Checkpoint Inhibitors in Cancer Therapy-How to Overcome Drug Resistance?. Cancers, 14.","DOI":"10.3390\/cancers14153575"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.3390\/curroncol29050247","article-title":"Immune Checkpoint Inhibitors in Cancer Therapy","volume":"29","author":"Shiravand","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Iranzo, P., Callejo, A., Assaf, J.D., Molina, G., Lopez, D.E., Garcia-Illescas, D., Pardo, N., Navarro, A., Martinez-Marti, A., and Cedres, S. (2022). Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer. Front. Med., 9.","DOI":"10.3389\/fmed.2022.875974"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Yazdani, H.O., Morder, K., Geller, D.A., Simmons, R.L., and Tohme, S. (2021). Neutrophil Extracellular Traps Promote T Cell Exhaustion in the Tumor Microenvironment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.785222"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e009082","DOI":"10.1136\/jitc-2024-009082","article-title":"Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis","volume":"12","author":"Zhou","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.immuni.2024.01.010","article-title":"LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation","volume":"57","author":"Joller","year":"2024","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.cell.2018.11.010","article-title":"Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3","volume":"176","author":"Wang","year":"2019","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e000957","DOI":"10.1136\/jitc-2020-000957","article-title":"TIGIT in cancer immunotherapy","volume":"8","author":"Chauvin","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.jhep.2010.07.044","article-title":"Intratumoral neutrophils: A poor prognostic factor for hepatocellular carcinoma following resection","volume":"54","author":"Li","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shen, M., Hu, P., Donskov, F., Wang, G., Liu, Q., and Du, J. (2014). Tumor-associated neutrophils as a new prognostic factor in cancer: A systematic review and meta-analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098259"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Boone, B.A., Murthy, P., Miller-Ocuin, J., Doerfler, W.R., Ellis, J.T., Liang, X., Ross, M.A., Wallace, C.T., Sperry, J.L., and Lotze, M.T. (2018). Chloroquine reduces hypercoagulability in pancreatic cancer through inhibition of neutrophil extracellular traps. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4584-2"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, R., Zhu, C., Zhao, J., and Tian, Y. (2026). Tumor-associated neutrophils and survival outcomes in colorectal cancer: A systematic review and multilevel meta-analysis. Front. Oncol., 16.","DOI":"10.3389\/fonc.2026.1788605"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e70614","DOI":"10.1002\/cam4.70614","article-title":"The Prognostic Value of Tumor-Associated Neutrophils in Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"14","author":"Jiang","year":"2025","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Thalin, C., Lundstrom, S., Seignez, C., Daleskog, M., Lundstrom, A., Henriksson, P., Helleday, T., Phillipson, M., Wallen, H., and Demers, M. (2018). Citrullinated histone H3 as a novel prognostic blood marker in patients with advanced cancer. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191231"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/bjh.15906","article-title":"Citrullinated histone H3, a biomarker for neutrophil extracellular trap formation, predicts the risk of mortality in patients with cancer","volume":"186","author":"Grilz","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yan, B., Dai, X., Ma, Q., and Wu, X. (2021). Stromal Neutrophil Extracellular Trap Density Is an Independent Prognostic Factor for Cervical Cancer Recurrence. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.659445"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1152\/physrev.00062.2021","article-title":"Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases","volume":"103","author":"Herre","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Saffarzadeh, M., Juenemann, C., Queisser, M.A., Lochnit, G., Barreto, G., Galuska, S.P., Lohmeyer, J., and Preissner, K.T. (2012). Neutrophil extracellular traps directly induce epithelial and endothelial cell death: A predominant role of histones. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032366"},{"key":"ref_29","first-page":"7095902","article-title":"NOX2-Derived Reactive Oxygen Species in Cancer","volume":"2020","author":"Aydin","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/s43018-022-00468-w","article-title":"The cGAS-STING pathway and cancer","volume":"3","author":"Samson","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41418-018-0261-x","article-title":"To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps","volume":"26","author":"Boeltz","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13054-025-05283-0","article-title":"\u201cThe NET effect\u201d: Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis","volume":"29","author":"Retter","year":"2025","journal-title":"Crit. Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"Papayannopoulos","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20100239","article-title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps","volume":"207","author":"Li","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115001","DOI":"10.1016\/j.jep.2022.115001","article-title":"Ganluyin ameliorates DSS-induced ulcerative colitis by inhibiting the enteric-origin LPS\/TLR4\/NF-\u03baB pathway","volume":"289","author":"Xiong","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo","volume":"18","author":"Yipp","year":"2012","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7413","DOI":"10.4049\/jimmunol.1000675","article-title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus","volume":"185","author":"Pilsczek","year":"2010","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/cdd.2009.96","article-title":"Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps","volume":"16","author":"Yousefi","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaar6676","DOI":"10.1126\/sciimmunol.aar6676","article-title":"Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps","volume":"3","author":"Chen","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"eaar6689","DOI":"10.1126\/sciimmunol.aar6689","article-title":"Gasdermin D plays a vital role in the generation of neutrophil extracellular traps","volume":"3","author":"Sollberger","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1002\/eji.201545772","article-title":"Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux","volume":"45","author":"Ruhl","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1600-065X.2007.00573.x","article-title":"The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy","volume":"220","author":"Apetoh","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.devcel.2017.10.013","article-title":"Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps","volume":"43","author":"Amulic","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.immuni.2020.03.001","article-title":"CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity","volume":"52","author":"Teijeira","year":"2020","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nm1565","article-title":"Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood","volume":"13","author":"Clark","year":"2007","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11037","DOI":"10.1038\/ncomms11037","article-title":"Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis","volume":"7","author":"Guglietta","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1158\/0008-5472.CAN-21-4045","article-title":"A Novel Selective Inhibitor JBI-589 Targets PAD4-Mediated Neutrophil Migration to Suppress Tumor Progression","volume":"82","author":"Deng","year":"2022","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1016\/j.celrep.2019.05.091","article-title":"Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis","volume":"27","author":"Hsu","year":"2019","journal-title":"Cell Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Behnen, M., Moller, S., Brozek, A., Klinger, M., and Laskay, T. (2017). Extracellular Acidification Inhibits the ROS-Dependent Formation of Neutrophil Extracellular Traps. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00184"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.7150\/thno.104557","article-title":"Tumor-derived exosomes induce neutrophil infiltration and reprogramming to promote T-cell exhaustion in hepatocellular carcinoma","volume":"15","author":"Bi","year":"2025","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102577","DOI":"10.1016\/j.jbc.2022.102577","article-title":"DNA-mediated proteolysis by neutrophil elastase enhances binding activities of the HMGB1 protein","volume":"298","author":"Wang","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e128008","DOI":"10.1172\/jci.insight.128008","article-title":"Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects","volume":"4","author":"Rayes","year":"2019","journal-title":"JCI Insight"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"154","DOI":"10.20892\/j.issn.2095-3941.2019.0353","article-title":"Neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1\/RAGE\/IL-8 axis","volume":"17","author":"Zha","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Martins-Cardoso, K., Almeida, V.H., Bagri, K.M., Rossi, M.I.D., Mermelstein, C.S., Konig, S., and Monteiro, R.Q. (2020). Neutrophil Extracellular Traps (NETs) Promote Pro-Metastatic Phenotype in Human Breast Cancer Cells through Epithelial-Mesenchymal Transition. Cancers, 12.","DOI":"10.3390\/cancers12061542"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nm.4027","article-title":"Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease","volume":"22","author":"Lood","year":"2016","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1073\/pnas.1414055112","article-title":"SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx","volume":"112","author":"Douda","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.trecan.2025.06.010","article-title":"mtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression","volume":"11","author":"Canadas","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/ijc.33205","article-title":"The roles of PAD2- and PAD4-mediated protein citrullination catalysis in cancers","volume":"148","author":"Wang","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.tcb.2022.01.014","article-title":"Insights into peptidylarginine deiminase expression and citrullination pathways","volume":"32","author":"Yu","year":"2022","journal-title":"Trends Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ostrowska-Podhorodecka, Z., Ding, I., Norouzi, M., and McCulloch, C.A. (2022). Impact of Vimentin on Regulation of Cell Signaling and Matrix Remodeling. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.869069"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rappu, P., Suwal, U., Siljamaki, E., and Heino, J. (2022). Inflammation-related citrullination of matrisome proteins in human cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1035188"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1038\/s41467-018-07306-7","article-title":"Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix","volume":"9","author":"Yuzhalin","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1158\/1541-7786.MCR-24-1095","article-title":"PAD2-Mediated Histone Citrullination Drives Tumor Progression by Enhancing Cell Proliferation and Modifying the Microenvironment in Pancreatic Cancer","volume":"23","author":"Umemura","year":"2025","journal-title":"Mol. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature04515","article-title":"Cryopyrin activates the inflammasome in response to toxins and ATP","volume":"440","author":"Mariathasan","year":"2006","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature07725","article-title":"AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC","volume":"458","author":"Hornung","year":"2009","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nature07710","article-title":"AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA","volume":"458","author":"Yu","year":"2009","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"eaao4227","DOI":"10.1126\/science.aao4227","article-title":"Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice","volume":"361","author":"Albrengues","year":"2018","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41586-020-2394-6","article-title":"DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25","volume":"583","author":"Yang","year":"2020","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mancini, S.J.C., Balabanian, K., Corre, I., Gavard, J., Lazennec, G., Le Bousse-Kerdiles, M.C., Louache, F., Maguer-Satta, V., Mazure, N.M., and Mechta-Grigoriou, F. (2021). Deciphering Tumor Niches: Lessons from Solid and Hematological Malignancies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.766275"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.7150\/thno.111096","article-title":"Targeting neutrophil extracellular traps in cancer progression and metastasis","volume":"15","author":"Zhang","year":"2025","journal-title":"Theranostics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.jhep.2021.07.032","article-title":"Regulatory T-cell and neutrophil extracellular trap interaction contributes to carcinogenesis in non-alcoholic steatohepatitis","volume":"75","author":"Wang","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41577-019-0257-x","article-title":"B cells, plasma cells and antibody repertoires in the tumour microenvironment","volume":"20","author":"Sharonov","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5626","DOI":"10.1158\/0008-5472.CAN-19-0800","article-title":"Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth","volume":"79","author":"Yazdani","year":"2019","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1172\/JCI67484","article-title":"Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis","volume":"123","author":"Spicer","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1002\/ijc.30635","article-title":"Neutrophil extracellular traps sequester circulating tumor cells via beta1-integrin mediated interactions","volume":"140","author":"Najmeh","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41416-025-03192-1","article-title":"Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1\/2 pathway promote chemoresistance in pancreatic cancer","volume":"133","author":"Nogi","year":"2025","journal-title":"Br. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s00262-025-03946-z","article-title":"Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: Potential suppression by pirfenidone","volume":"74","author":"Yagi","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13076","DOI":"10.1073\/pnas.1200419109","article-title":"Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis","volume":"109","author":"Demers","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1136\/annrheumdis-2015-208356","article-title":"Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs","volume":"75","author":"Corsiero","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41586-019-1914-8","article-title":"Tertiary lymphoid structures improve immunotherapy and survival in melanoma","volume":"577","author":"Cabrita","year":"2020","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2147\/JHC.S303588","article-title":"The Crosstalk Between Cancer Cells and Neutrophils Enhances Hepatocellular Carcinoma Metastasis via Neutrophil Extracellular Traps-Associated Cathepsin G Component: A Potential Therapeutic Target","volume":"8","author":"Guan","year":"2021","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Xin, H., Lai, Q., Zhou, Y., He, J., Song, Y., Liao, M., Sun, J., Li, M., Zhang, M., and Liang, W. (2023). Noninvasive evaluation of neutrophil extracellular traps signature predicts clinical outcomes and immunotherapy response in hepatocellular carcinoma. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134521"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13046-024-03122-8","article-title":"CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN\/AKT signaling phosphorylation and neutrophil chemotaxis","volume":"43","author":"Sun","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e20190354","DOI":"10.1084\/jem.20190354","article-title":"Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer","volume":"217","author":"Zhang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1038\/s41467-021-23086-z","article-title":"Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer","volume":"12","author":"Mansure","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1158\/1078-0432.CCR-24-1363","article-title":"NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance","volume":"30","author":"Mowery","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.7150\/jca.64170","article-title":"Neutrophil extracellular traps in hepatocellular carcinoma are enriched in oxidized mitochondrial DNA which is highly pro-inflammatory and pro-metastatic","volume":"13","author":"Yang","year":"2022","journal-title":"J. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e012736","DOI":"10.1136\/jitc-2025-012736","article-title":"Neutrophil extracellular traps-STC1 positive feedback loop promotes immune evasion and metastasis in bladder cancer","volume":"13","author":"Cai","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1111\/febs.17144","article-title":"A combined model of serum neutrophil extracellular traps, CD8+ T cells, and tumor proportion score provides better prediction of PD-1 inhibitor efficacy in patients with NSCLC","volume":"291","author":"Guo","year":"2024","journal-title":"FEBS J."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ding, W., Li, B., Zhang, Y., He, L., and Su, J. (2022). A neutrophil extracellular traps-associated lncRNA signature predicts the clinical outcomes in patients with lung adenocarcinoma. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.1047231"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wang, Y., Onuma, A., He, J., Wang, H., Xia, Y., Lal, R., Cheng, X., Kasumova, G., and Hu, Z. (2021). Neutrophils Extracellular Traps Inhibition Improves PD-1 Blockade Immunotherapy in Colorectal Cancer. Cancers, 13.","DOI":"10.3390\/cancers13215333"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"15","DOI":"10.32607\/actanaturae.11503","article-title":"Neutrophil Extracellular Traps (NETs): Opportunities for Targeted Therapy","volume":"13","author":"Volkov","year":"2021","journal-title":"Acta Naturae"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s40164-025-00670-3","article-title":"Exploring neutrophil extracellular traps: Mechanisms of immune regulation and future therapeutic potential","volume":"14","author":"Gao","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yan, M., Gu, Y., Sun, H., and Ge, Q. (2023). Neutrophil extracellular traps in tumor progression and immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1135086"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"361ra138","DOI":"10.1126\/scitranslmed.aag1711","article-title":"Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps","volume":"8","author":"Park","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.ccell.2020.12.012","article-title":"Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation","volume":"39","author":"Xiao","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e69257","DOI":"10.7554\/eLife.69257","article-title":"Neutrophil extracellular traps arm DC vaccination against NPM-mutant myeloproliferation","volume":"11","author":"Tripodo","year":"2022","journal-title":"eLife"},{"key":"ref_104","first-page":"102","article-title":"Lipid nanoparticle used in mRNA vaccine promotes tumor metastasis in mouse model via mtDNA-induced neutrophil activation and NETosis","volume":"64","author":"Wang","year":"2026","journal-title":"Nano Today"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e000326","DOI":"10.1136\/jitc-2019-000326","article-title":"Simultaneous inhibition of CXCR1\/2, TGF-beta, and PD-L1 remodels the tumor and its microenvironment to drive antitumor immunity","volume":"8","author":"Horn","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"121506","DOI":"10.1016\/j.biomaterials.2022.121506","article-title":"Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma","volume":"284","author":"Cheng","year":"2022","journal-title":"Biomaterials"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jconrel.2023.04.013","article-title":"Cell membrane derived liposomes loaded with DNase I target neutrophil extracellular traps which inhibits colorectal cancer liver metastases","volume":"357","author":"Wang","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Zhu, D., Lu, Y., Wang, Y., and Wang, Y. (2022). PAD4 and Its Inhibitors in Cancer Progression and Prognosis. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112414"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Shahzad, M.H., Feng, L., Su, X., Brassard, A., Dhoparee-Doomah, I., Ferri, L.E., Spicer, J.D., and Cools-Lartigue, J.J. (2022). Neutrophil Extracellular Traps in Cancer Therapy Resistance. Cancers, 14.","DOI":"10.3390\/cancers14051359"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e3530","DOI":"10.1002\/jgm.3530","article-title":"GSK484, an inhibitor of peptidyl arginine deiminase 4, increases the radiosensitivity of colorectal cancer and inhibits neutrophil extracellular traps","volume":"25","author":"Wang","year":"2023","journal-title":"J. Gene Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1158\/1535-7163.MCT-19-1020","article-title":"A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma","volume":"19","author":"Li","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"59683","DOI":"10.1021\/acsami.1c18660","article-title":"Tumor-Associated Neutrophil Extracellular Traps Regulating Nanocarrier-Enhanced Inhibition of Malignant Tumor Growth and Distant Metastasis","volume":"13","author":"Yin","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13058-019-1243-8","article-title":"A window-of-opportunity trial of the CXCR1\/2 inhibitor reparixin in operable HER-2-negative breast cancer","volume":"22","author":"Goldstein","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molmed.2023.09.003","article-title":"CXCR2 chemokine receptor\u2014A master regulator in cancer and physiology","volume":"30","author":"Lazennec","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.canlet.2021.12.027","article-title":"Complement C5a induces the formation of neutrophil extracellular traps by myeloid-derived suppressor cells to promote metastasis","volume":"529","author":"Morales","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1021\/acsptsci.1c00227","article-title":"In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy","volume":"5","author":"Cui","year":"2022","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2261242","DOI":"10.1080\/2162402X.2023.2261242","article-title":"C5aR1 blockade reshapes immunosuppressive tumor microenvironment and synergizes with immune checkpoint blockade therapy in high-grade serous ovarian cancer","volume":"12","author":"Zhang","year":"2023","journal-title":"OncoImmunology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.imlet.2005.03.003","article-title":"The C3a receptor antagonist SB 290157 has agonist activity","volume":"100","author":"Mathieu","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00280-019-03988-y","article-title":"Small molecule inhibitor of TLR4 inhibits ovarian cancer cell proliferation: New insight into the anticancer effect of TAK-242 (Resatorvid)","volume":"85","author":"Kashani","year":"2020","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_120","first-page":"1146","article-title":"Platelet glycoprotein VI promotes metastasis through interaction with cancer cell-derived galectin-3","volume":"135","author":"Sarukhanyan","year":"2020","journal-title":"Blood"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Darbousset, R., Senkpeil, L., Kuehn, J., Balu, S., Miglani, D., Dillon, E., Fromson, C., Elahee, M., Jarrot, P.A., and Montesi, S.B. (2025). A GPVI-platelet-neutrophil-NET axis drives systemic sclerosis. bioRxiv.","DOI":"10.1101\/2025.01.21.634123"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1056\/NEJMoa1611770","article-title":"Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease","volume":"376","author":"Ataga","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.semcancer.2010.04.005","article-title":"Selectins promote tumor metastasis","volume":"20","author":"Laubli","year":"2010","journal-title":"Semin. Cancer Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"108730","DOI":"10.1016\/j.intimp.2022.108730","article-title":"Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1\/TLR9 pathways and neutrophils extracellular traps formation","volume":"108","author":"Gu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41389-020-00267-x","article-title":"Tumor-derived HMGB1 induces CD62L(dim) neutrophil polarization and promotes lung metastasis in triple-negative breast cancer","volume":"9","author":"Wang","year":"2020","journal-title":"Oncogenesis"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12672-024-01010-3","article-title":"Targeting neutrophil elastase is a promising direction for future cancer treatment","volume":"15","author":"Jia","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1111\/j.1349-7006.2006.00278.x","article-title":"Sivelestat, a specific neutrophil elastase inhibitor, suppresses the growth of gastric carcinoma cells by preventing the release of transforming growth factor-\u03b1","volume":"97","author":"Wada","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1158\/1535-7163.MCT-23-0414","article-title":"Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis","volume":"23","author":"Lulla","year":"2024","journal-title":"Mol. Cancer Ther."},{"key":"ref_129","first-page":"111","article-title":"A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium","volume":"9","author":"Vogelmeier","year":"2012","journal-title":"COPD J. Chronic Obstr. Pulm. Dis."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Santos Bonilha, C., and Protasio Veras, F. (2026). Mapping benefit, risk, and opportunity in PAD4 inhibition. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1769421"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Teesalu, T., Sugahara, K.N., and Ruoslahti, E. (2013). Tumor-penetrating peptides. Front. Oncol., 3.","DOI":"10.3389\/fonc.2013.00216"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Dich, H., Abou Rjeily, R., Rath, G., Berthet, M., Dayde-Cazals, B., Berret, J.F., and Angles-Cano, E. (2025). Dual-functional cerium oxide nanoparticles with antioxidant and DNase I activities to prevent and degrade neutrophil extracellular traps. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1693809"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Hong, W., Ye, X., Chen, L., Chai, X., Yin, Y., Li, Z., Fang, C., Qian, X., Yu, B., and Qin, G. (2025). Prognostic value of tumour-associated neutrophils in different polarization status releasing neutrophil extracellular traps in the immunotherapy of advanced non-small cell lung cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1705716"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1186\/s12967-026-08227-6","article-title":"Integrative single-cell and spatial multi-Omics analyses identify NETs-driven colon cancer subtypes with distinct metabolic features and prognostic implications","volume":"24","author":"Tang","year":"2026","journal-title":"J. Transl. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41698-024-00586-x","article-title":"Multiomics integration reveals NETosis heterogeneity and TLR2 as a prognostic biomarker in pancreatic cancer","volume":"8","author":"Fu","year":"2024","journal-title":"npj Precis. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"102651","DOI":"10.1016\/j.tranon.2025.102651","article-title":"Single-cell mapping of neutrophil extracellular trap signatures in lung adenocarcinoma reveals immune landscapes, prognostic potential, and therapeutic targets","volume":"64","author":"Liu","year":"2026","journal-title":"Transl. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e70194","DOI":"10.1002\/eji.70194","article-title":"Mapping of Neutrophils in Cancers: Insights from Spatial Omics Technologies","volume":"56","author":"Li","year":"2026","journal-title":"Eur. J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:03:10Z","timestamp":1789639390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":137,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188278"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188278","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}