{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:03:24Z","timestamp":1791644604440,"version":"4.3.4"},"reference-count":71,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R01CA228524"],"award-info":[{"award-number":["R01CA228524"]}]},{"name":"National Cancer Institute","award":["P30CA036727"],"award-info":[{"award-number":["P30CA036727"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Distinguished Professorship of Pathology and Microbiology Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Tumor-promoting inflammation and immune evasion are hallmarks of cancer, contributing to the survival and proliferation of tumor cells. Infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME) often cause this inflammation and immune evasion. Neutrophils are leukocytes that contribute to inflammation and have immunomodulatory functions. They are shown to have pro- or anti-tumorigenic roles contingent on cancer type. Methods: In this study, we examined the role of neutrophil recruitment in pancreatic cancer (PC) progression using patient samples and murine models. Results: We observed enhanced neutrophil infiltration and neutrophil extracellular trap (NET) formation, which were dependent on disease stage and tumor site. Our murine model studies showed that the infiltration of neutrophils and NETs was dependent on disease progression. Moreover, chemokine receptor CXCR2 and its ligands played a crucial role in neutrophil recruitment. The expression of CXCR2 and its ligands was associated with a worse prognosis for patients. Conclusions: Our data demonstrates that gemcitabine therapy enhances neutrophil recruitment and NET formation in PC. In addition, we observed altered neutrophil phenotypes in PC dependent on disease progression, suggesting a context-dependent immunomodulatory role. Together, our data demonstrate that CXCR2-driven neutrophil recruitment increases with PC progression, is enhanced by gemcitabine chemotherapy, promotes an immunosuppressive microenvironment, and is associated with poor patient survival.<\/jats:p>","DOI":"10.3390\/cancers17213541","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:40:48Z","timestamp":1762180848000},"page":"3541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neutrophil Dynamics Contribute to Disease Progression and Poor Survival in Pancreatic Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6743-9723","authenticated-orcid":false,"given":"Reegan","family":"Sturgeon","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, The University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6494-632X","authenticated-orcid":false,"given":"Paran","family":"Goel","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, The University of Alabama, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Molczyk","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, The University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridhi","family":"Bhola","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, The University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Grandgenett","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Hollingsworth","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-3520","authenticated-orcid":false,"given":"Rakesh K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, The University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jbior.2017.11.007","article-title":"Molecular and cellular mechanisms of chemoresistance in pancreatic cancer","volume":"68","author":"Adamska","year":"2018","journal-title":"Adv. Biol. Regul."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/nm.3291","article-title":"An interleukin-17\u2013mediated paracrine network promotes tumor resistance to anti-angiogenic therapy","volume":"19","author":"Chung","year":"2013","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4251\/wjgo.v9.i1.37","article-title":"Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer","volume":"9","author":"Elaskalani","year":"2017","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.18632\/oncotarget.13907","article-title":"The role of tumor microenvironment in therapeutic resistance","volume":"8","author":"Son","year":"2017","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrd1984","article-title":"Targeting multidrug resistance in cancer","volume":"5","author":"Szakacs","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nrgastro.2010.188","article-title":"Pancreatic cancer: Understanding and overcoming chemoresistance","volume":"8","author":"Wang","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7178","DOI":"10.7150\/thno.43093","article-title":"Inflammatory IFIT3 renders chemotherapy resistance by regulating post-translational modification of VDAC2 in pancreatic cancer","volume":"10","author":"Wang","year":"2020","journal-title":"Theranostics"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zeng, S., P\u00f6ttler, M., Lan, B., Gr\u00fctzmann, R., Pilarsky, C., and Yang, H. (2019). Chemoresistance in Pancreatic Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184504"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature16064","article-title":"Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer","volume":"527","author":"Zheng","year":"2015","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4251\/wjgo.v12.i2.173","article-title":"Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy","volume":"12","author":"Sarantis","year":"2020","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/carcin\/bgp127","article-title":"Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability","volume":"30","author":"Colotta","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/ijc.24409","article-title":"Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms","volume":"125","author":"McDonald","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Padoan, A., Plebani, M., and Basso, D. (2019). Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030676"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and tumor progression: Signaling pathways and targeted intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.micinf.2003.09.008","article-title":"Neutrophil granules and secretory vesicles in inflammation","volume":"5","author":"Faurschou","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/JID.2015.410","article-title":"Neutrophils Self-Regulate Immune Complex-Mediated Cutaneous Inflammation through CXCL2","volume":"136","author":"Li","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/imm.12545","article-title":"Interleukin-23 (IL-23), independent of IL-17 and IL-22, drives neutrophil recruitment and innate inflammation during Clostridium difficile colitis in mice","volume":"147","author":"McDermott","year":"2016","journal-title":"Immunology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rosales, C. (2018). Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00113"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41392-024-02049-y","article-title":"Neutrophil diversity and function in health and disease","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Figueroa, E., \u00c1lvarez-Carrasco, P., Ortega, E., and Maldonado-Bernal, C. (2021). Neutrophils: Many Ways to Die. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.631821"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.immuni.2021.06.006","article-title":"The Neutrophil","volume":"54","author":"Burn","year":"2021","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/978-1-4939-9424-3_31","article-title":"Neutrophil Extracellular Traps","volume":"1982","author":"Rada","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14355","DOI":"10.1007\/s13277-016-5328-z","article-title":"NETs in cancer","volume":"37","author":"Garley","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/abbs\/gmy104","article-title":"Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer","volume":"50","author":"Niu","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","unstructured":"McDonald, P.C., Topham, J.T., Awrey, S., Tavakoli, H., Carroll, R., Brown, W.S., Gerbec, Z.J., Kalloger, S.E., Karasinska, J.M., and Tang, P. (2025). Neutrophil extracellular trap gene expression signatures identify prognostic and targetable signaling axes for inhibiting pancreatic tumour metastasis. Commun. Biol., 8.","DOI":"10.1038\/s42003-025-08440-x"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mitsis, M., Drosou, P., Tatsis, V., and Markopoulos, G.S. (2022). Neutrophil Extracellular Traps and Pancreatic Cancer Development: A Vicious Cycle. Cancers, 14.","DOI":"10.3390\/cancers14143339"},{"key":"ref_30","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_31","doi-asserted-by":"crossref","unstructured":"Demkow, U. (2021). Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis. Cancers, 13.","DOI":"10.3390\/cancers13174495"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.1111\/jcmm.16555","article-title":"Neutrophil extracellular DNA traps promote pancreatic cancer cells migration and invasion by activating EGFR\/ERK pathway","volume":"25","author":"Jin","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Simmons, R.L., Tohme, S., and Yazdani, H.O. (2021). Neutrophil Extracellular Traps (NETs) in Cancer Metastasis. Cancers, 13.","DOI":"10.3390\/cancers13236131"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Masucci, M.T., Minopoli, M., Del Vecchio, S., and Carriero, M.V. (2020). The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01749"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nogi, S., Kagawa, S., Taniguchi, A., Yagi, T., Kanaya, N., Kakiuchi, Y., Yasui, K., Fuji, T., Kono, Y., and Kikuchi, S. (2025). Gemcitabine-induced neutrophil extracellular traps via interleukin-8-CXCR1\/2 pathway promote chemoresistance in pancreatic cancer. Br. J. Cancer, 1\u201312.","DOI":"10.1038\/s41416-025-03192-1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2398725","DOI":"10.1080\/07853890.2024.2398725","article-title":"Prognostic value of neutrophil to lymphocyte ratio in patients with advanced pancreatic ductal adenocarcinoma treated with systemic chemotherapy","volume":"56","author":"Kitsugi","year":"2024","journal-title":"Ann. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.18632\/genesandcancer.171","article-title":"Desmoplasia in pancreatic ductal adenocarcinoma: Insight into pathological function and therapeutic potential","volume":"9","author":"Cannon","year":"2018","journal-title":"Genes Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41698-024-00681-z","article-title":"Barriers and opportunities in pancreatic cancer immunotherapy","volume":"8","author":"Ju","year":"2024","journal-title":"npj Precis. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.trecan.2022.03.004","article-title":"The interactive role of inflammatory mediators and metabolic reprogramming in pancreatic cancer","volume":"8","author":"Ohara","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Xiang, Z.-J., Hu, T., Wang, Y., Wang, H., Xu, L., and Cui, N. (2020). Neutrophil\u2013lymphocyte ratio (NLR) was associated with prognosis and immunomodulatory in patients with pancreatic ductal adenocarcinoma (PDAC). Biosci. Rep., 40.","DOI":"10.1042\/BSR20201190"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13046-021-01960-4","article-title":"ROS and TGF\u03b2: From pancreatic tumour growth to metastasis","volume":"40","author":"Chang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4839","DOI":"10.7150\/thno.56747","article-title":"The double-edged roles of ROS in cancer prevention and therapy","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Torres, M.P., Rachagani, S., Souchek, J.J., Mallya, K., Johansson, S.L., and Batra, S.K. (2013). Novel Pancreatic Cancer Cell Lines Derived from Genetically Engineered Mouse Models of Spontaneous Pancreatic Adenocarcinoma: Applications in Diagnosis and Therapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080580"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bartha, \u00c1., and Gy\u0151rffy, B. (2021). TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052622"},{"key":"ref_46","first-page":"100625","article-title":"Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors","volume":"5","year":"2024","journal-title":"Innovation"},{"key":"ref_47","first-page":"68","article-title":"Differential expression profile of CXC-receptor-2 ligands as potential biomarkers in pancreatic ductal adenocarcinoma","volume":"12","author":"Saxena","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1172\/JCI41649","article-title":"CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow","volume":"120","author":"Eash","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s10735-024-10260-y","article-title":"A key regulator of tumor-associated neutrophils: The CXCR2 chemokine receptor","volume":"55","author":"Kang","year":"2024","journal-title":"Histochem. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/MOH.0000000000000476","article-title":"The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics","volume":"26","author":"Zhang","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Molczyk, C., and Singh, R.K. (2023). CXCR1: A Cancer Stem Cell Marker and Therapeutic Target in Solid Tumors. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020576"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"216185","DOI":"10.1016\/j.canlet.2023.216185","article-title":"Small molecule antagonist of CXCR2 and CXCR1 inhibits tumor growth, angiogenesis, and metastasis in pancreatic cancer","volume":"563","author":"Prajapati","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.21873\/invivo.12155","article-title":"The Effect of Gemcitabine on Cell Cycle Arrest and microRNA Signatures in Pancreatic Cancer Cells","volume":"34","author":"Namima","year":"2020","journal-title":"Vivo"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9405","DOI":"10.1096\/fj.201902990R","article-title":"CXCR2 signaling promotes secretory cancer-associated fibroblasts in pancreatic ductal adenocarcinoma","volume":"34","author":"Awaji","year":"2020","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1593\/tlo.10184","article-title":"CXCR2-Dependent Endothelial Progenitor Cell Mobilization in Pancreatic Cancer Growth","volume":"4","author":"Li","year":"2011","journal-title":"Transl. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.ajpath.2021.01.002","article-title":"Host Cxcr2-Dependent Regulation of Pancreatic Cancer Growth, Angiogenesis, and Metastasis","volume":"191","author":"Purohit","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7280","DOI":"10.18632\/oncotarget.6906","article-title":"CXCR2 signaling regulates KRAS(G12D)-induced autocrine growth of pancreatic cancer","volume":"7","author":"Purohit","year":"2016","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/annonc\/mdu587","article-title":"Baseline neutrophil\u2013lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use","volume":"26","author":"Lorente","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wu, L., Saxena, S., Goel, P., Prajapati, D.R., Wang, C., and Singh, R.K. (2020). Breast Cancer Cell\u2013Neutrophil Interactions Enhance Neutrophil Survival and Pro-Tumorigenic Activities. Cancers, 12.","DOI":"10.3390\/cancers12102884"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1182\/blood.V93.7.2173","article-title":"Metalloproteinases are involved in lipopolysaccharide- and tumor necrosis factor-alpha-mediated regulation of CXCR1 and CXCR2 chemokine receptor expression","volume":"93","author":"Khandaker","year":"1999","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.mvr.2011.06.011","article-title":"CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation","volume":"82","author":"Singh","year":"2011","journal-title":"Microvasc. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13058-015-0527-x","article-title":"Inhibition of iNOS as a novel effective targeted therapy against triple-negative breast cancer","volume":"17","author":"Liu","year":"2015","journal-title":"Breast Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.redox.2015.08.009","article-title":"The dual role of iNOS in cancer","volume":"6","author":"Vannini","year":"2015","journal-title":"Redox Biol."},{"key":"ref_64","first-page":"e129756","article-title":"Regulatory T cells use arginase 2 to enhance their metabolic fitness in tissues","volume":"4","author":"Lowe","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1111\/j.1476-5381.2009.00291.x","article-title":"Arginase: An emerging key player in the mammalian immune system","volume":"158","author":"Munder","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Vonwirth, V., B\u00fclb\u00fcl, Y., Werner, A., Echchannaoui, H., Windschmitt, J., Habermeier, A., Ioannidis, S., Shin, N., Conradi, R., and Bros, M. (2021). Inhibition of Arginase 1 Liberates Potent T Cell Immunostimulatory Activity of Human Neutrophil Granulocytes. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.617699"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/ijc.28770","article-title":"Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17\u2014A new mechanism of impaired antitumor immunity","volume":"135","author":"Mishalian","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/imr.13162","article-title":"Neutrophil\u2014T cell crosstalk and the control of the host inflammatory response","volume":"314","author":"Bert","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.pharmthera.2019.05.012","article-title":"Cellular determinants and therapeutic implications of inflammation in pancreatic cancer","volume":"201","author":"Stone","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"112788","DOI":"10.1016\/j.intimp.2024.112788","article-title":"Neutrophils\u2019 dual role in cancer: From tumor progression to immunotherapeutic potential","volume":"140","author":"Wu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_71","first-page":"1163","article-title":"Neutrophils in cancer: Dual roles through intercellular interactions","volume":"43","author":"Yu","year":"2024","journal-title":"Oncogene"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:24:32Z","timestamp":1762233872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":71,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17213541"],"URL":"https:\/\/doi.org\/10.3390\/cancers17213541","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}