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By integrating roles of TME immune composition and neutrophil polarization, the article highlights implications for metastases and resistance to therapy.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/neutrophil-plasticity-and-netosis-in-tumour-microenvironment-tumour-evolution-and-therapy-resistance/444197/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/neutrophil-plasticity-and-netosis-in-tumour-microenvironment-tumour-evolution-and-therapy-resistance/444197.png","ImageObject",300,407,{"name":42,"@type":43},"Đào","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are NETs and what is NETosis in the context of cancer?","Question",{"text":63,"@type":64},"NETs are DNA-histone web-like structures with associated proteins released by activated neutrophils. NETosis is the process of NET formation, and the review links NETosis to tumour progression and malignant spread.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do tumour-associated neutrophils (TANs) relate to prognosis?",{"text":68,"@type":64},"The review notes that TANs can exert both anti-tumour and pro-tumour functions through different interactions. However, in many human tumours, a high TAN density correlates with poor prognosis, likely via pro-tumour inflammation.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the tumour microenvironment (TME) influence neutrophil behaviour?",{"text":72,"@type":64},"The TME is described as a heterogeneous ecosystem containing tumour, stromal, and immune cells. 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M. Sullman,2,3 Hamed Fouladseresht , 1 and Nahid Eskandari 1,4  \n1Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran  \n2Department of Social Sciences, University of Nicosia, Nicosia, Cyprus  \n3Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus  \n4Department of Immunology, Applied Physiology Research Center, Cardiovascular Research Institute,  \nIsfahan University of Medical Sciences, Isfahan, Iran  \nCorrespondence should be addressed to Nahid Eskandari; [neskandari@med.mui.ac.ir](neskandari@med.mui.ac.ir)  \nReceived 23 April 2025; Revised 1 November 2025; Accepted 5 December 2025  \nAcademic Editor: Poorani Gurumallesh  \nCopyright © 2026 Mojdeh Soltani et al. Journal of Immunology Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nNeutrophil extracellular traps (NETs) are web-like formations consisting of DNA-histone complexes and associated proteins released from activated neutrophils. While NET formation plays an important role in innate immunity, it is also associated with the pathogenesis of autoimmune disorders such as rheumatoid arthritis, psoriasis and systemic lupus erythematosus. Research suggests that NETosis (the process of NET formation) may contribute to the progression of cancer and the spread of malignant tumours. A clear link exists between the accumulation of neutrophils in the tumour microenvironment (TME), known as tumour-associated neutrophils (TANs) and NETosis activation in both primary and metastatic tumours. Furthermore, the literature highlights the role of NETs in modulating immune surveillance within the TME. This review aims to analyse the interplay between NETosis and the TME, emphasising its implications for tumour progression, immune evasion and resistance to therapy.  \nKeywords: immunotherapy; NETosis; neutrophil; tumour microenvironment  \n1. Introduction  \nThe tumour microenvironment (TME) is a heterogeneous ecosystem primarily consisting of tumour cells and stromal cells, such as vascular endothelial cells and cancer-associated fibroblasts (CAFs). Additionally, immune cells are crucial components ofthe TME, playing a significant role in either inhibiting or promoting cancer progression. Immune cells that inhibit tumour growth include effector T cells (such as CD4+ helper T cells and CD8+ cytotoxic T cells), natural killer (NK) cells, M1-polarised macrophages, dendritic cells (DC) and N1-polarised neutrophils. Conversely, immune cells that promote tumour growth include M2-polarised macrophages, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and N2-polarised neutrophils.  \nInnate immune cells shape the TME by secreting various mediators, such as cytokines, metabolites, chemokines and other factors. Histopathological analyses of the immune components within the TME—encompassing both innate and adaptive immune cells—are crucial for cancer diagnosis, staging and evaluating prognosis or treatment response.  \nNeutrophils, also referred to as polymorphonuclear leukocytes (PMNs), arise from the myeloid lineage and are the most common circulating white blood cells in mice and humans. They serve as the first responders during inflammation, infection and injury. Neutrophils capture invading microorganisms and pathogens through processes such as degranulation, phagocytosis and the formation of neutrophil extracellular traps (NETs). While they play an important role in responding  \n2 Journal of Immunolog","cbCaitKlYcUn7NdC","https://ap.wps.com/l/cbCaitKlYcUn7NdC","pdf",1326037,11,"English","# Introduction\n# Neutrophil Production and Its Migration to TME\n## Tumour microenvironment and immune components","[{\"question\":\"What are NETs and what is NETosis in the context of cancer?\",\"answer\":\"NETs are DNA-histone web-like structures with associated proteins released by activated neutrophils. NETosis is the process of NET formation, and the review links NETosis to tumour progression and malignant spread.\"},{\"question\":\"How do tumour-associated neutrophils (TANs) relate to prognosis?\",\"answer\":\"The review notes that TANs can exert both anti-tumour and pro-tumour functions through different interactions. However, in many human tumours, a high TAN density correlates with poor prognosis, likely via pro-tumour inflammation.\"},{\"question\":\"How does the tumour microenvironment (TME) influence neutrophil behaviour?\",\"answer\":\"The TME is described as a heterogeneous ecosystem containing tumour, stromal, and immune cells. Cytokine milieu and mediators within the TME can polarize neutrophils into N1 or N2 subtypes with distinct anti-tumoural versus pro-tumoural activities.\"}]","Neutrophil Plasticity and NETosis in Tumour Microenvironment - Tumour Evolution and Therapy Resistance | PDF",1790707205,28]