Academic Journal
Harnessing neutrophil plasticity: From mechanistic insights to oncology therapeutics.
| Title: | Harnessing neutrophil plasticity: From mechanistic insights to oncology therapeutics. |
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| Authors: | Zhang AQ; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China., Wang J; Army 953rd Hospital (Shigatse Branch, Xinqiao Hospital), Army Medical University, Shigatse, China., Chung JY; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China., Zhou J; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China., Tang PC; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China., Liu X; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China., Zhang Q; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China., To KF; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China., Li Y; Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, China. Electronic address: lys@cqu.edu.cn., Tang PM; Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong; CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Guangdong, China. Electronic address: patrick.tang@cuhk.edu.hk. |
| Source: | Cancer letters [Cancer Lett] 2026 Oct 10; Vol. 658, pp. 218730. Date of Electronic Publication: 2026 Jul 18. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
| MeSH Terms: | Neutrophils*/immunology , Neutrophils*/metabolism , Neutrophils*/drug effects , Tumor Microenvironment*/immunology , Neoplasms*/immunology , Neoplasms*/pathology , Neoplasms*/therapy , Cell Plasticity*, Extracellular Traps/immunology ; Extracellular Traps/metabolism ; Humans ; Animals ; Signal Transduction |
| Abstract: | Neutrophils are dynamic regulators of cancer progression rather than short-lived bystanders. Within the tumor microenvironment (TME), tumor-associated neutrophils (TANs) adopt heterogeneous, context-dependent states that extend far beyond the conventional N1/N2 dichotomy. Recent single-cell and spatial transcriptomic insights reveal that cytokine, stromal, metabolic, and epigenetic cues orchestrate this remarkable TAN plasticity. Once activated, TAN-derived proteases, reactive oxygen species, and neutrophil extracellular traps (NETs) drive angiogenesis, immune evasion, metastasis, and therapy resistance. Conversely, specific TAN subpopulations can directly kill tumor cells, present antigens, and synergize with adaptive immunity. This review synthesizes recent breakthroughs in TAN recruitment, heterogeneity, metabolic and epigenetic reprogramming, and cellular crosstalk. Furthermore, we evaluate therapeutic strategies targeting molecular signaling and NET formation, alongside emerging approaches to reprogram or engineer neutrophils, such as chimeric antigen receptor-engineered neutrophils (CAR-Ns). Finally, we address current barriers to clinical translation and outline how to achieve context-dependent modulation of neutrophil states to preserve essential host defenses during TAN-targeted oncology therapies. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cancer immunotherapy; Neutrophil extracellular traps; Neutrophil plasticity; Tumor microenvironment; Tumor-associated neutrophils |
| Entry Date(s): | Date Created: 20260718 Date Completed: 20260903 Latest Revision: 20260903 |
| Update Code: | 20260904 |
| DOI: | 10.1016/j.canlet.2026.218730 |
| PMID: | 42471044 |
| Database: | MEDLINE |
| ISSN: | 1872-7980 |
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| DOI: | 10.1016/j.canlet.2026.218730 |