Neutrophil Plasticity and NETosis in Tumour Microenvironment - Tumour Evolution and Therapy Resistance

Sep 29, 2026

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Neutrophil extracellular traps (NETs) are DNA-histone web-like structures released by activated neutrophils, and NETosis links innate immune activation to cancer biology. This review examines how tumour-associated neutrophils (TANs) and NETosis shape the tumour microenvironment (TME), influencing immune surveillance, tumour progression, and immune evasion. By integrating roles of TME immune composition and neutrophil polarization, the article highlights implications for metastases and resistance to therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

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Introduction

Neutrophil Production and Its Migration to TME

Tumour microenvironment and immune components

Wiley Journal of Immunology Research Volume 2026, Article ID 5568021, 11 pages [https://doi.org/10.1155/jimr/5568021](https://doi.org/10.1155/jimr/5568021) Review Article Neutrophil Plasticityand NETosisin Tumour Microenvironment: Tumour Evolution and Therapy Resistance Mojdeh Soltani , 1 Sara Falahi, 1 Mohammad Abbaszadeh, 1 Mark J. M. Sullman,2,3 Hamed Fouladseresht , 1 and Nahid Eskandari 1,4 1Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran 2Department of Social Sciences, University of Nicosia, Nicosia, Cyprus 3Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus 4Department of Immunology, Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran Correspondence should be addressed to Nahid Eskandari; [neskandari@med.mui.ac.ir](neskandari@med.mui.ac.ir) Received 23 April 2025; Revised 1 November 2025; Accepted 5 December 2025 Academic Editor: Poorani Gurumallesh Copyright © 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. Neutrophil 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. Keywords: immunotherapy; NETosis; neutrophil; tumour microenvironment 1. Introduction The 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. Innate 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. Neutrophils, 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 2 Journal of Immunolog

FAQs

What are NETs and what is NETosis in the context of cancer?

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.

How do tumour-associated neutrophils (TANs) relate to prognosis?

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.

How does the tumour microenvironment (TME) influence neutrophil behaviour?

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.

Sep 29, 2026

Uploaded by Đào