ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Prognostic value of tumour-associated neutrophils in different polarization status releasing neutrophil extracellular traps in the immunotherapy of advanced non-small cell lung cancer
Provisionally accepted
Weiwei Hong1
Xin Ye1Lin Chen2Xiangzhi Chai1Yan Yin1Zhaoqing Li1Chen Fang1Xiaoying Qian1Biao Yu1Guizhen Qin1Xinyuan Yao1Bingbiao Zhou1Chuanhong Luo1Chengsi Shu1Dengying Chen1
Yong Li1Yong Wang1*- 1The First Affiliated Hospital of Nanchang University, Nanchang, China
- 2Nanchang University Second Affiliated Hospital, Nanchang, China
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Purpose: This study analyzed the polarization types of tumour-associated neutrophils (TANs) that release neutrophil extracellular traps (NETs), as well as the impact of neutrophil polarization on the efficacy of immunotherapy for non-small cell lung cancer (NSCLC). Methods: This study retrospectively collected clinical data and pathological samples of 115 patients with advanced NSCLC who underwent first-line immunotherapy. Multiplex immunofluorescence staining was used to assess TANs polarization status and NETs expression. Results: We found that the presence of NETs was negatively associated with tumour-associated N1 neutrophil (P<0.001) but positively associated with tumour-associated N2 neutrophil (P<0.001). Further analysis revealed that the NETs-low group experienced prolonged progression-free survival (PFS) (15.0 vs 9.9 months, P=0.045) and overall survival (OS) (40.5 vs 22.0 months, P=0.002) with first-line immunotherapy compared with the NETs-high group. We also found that there was no significant difference in the efficacy of immunotherapy between those with tumour-associated N1 neutrophils exhibiting low NETs and those exhibiting high NETs. However, patients with tumour-associated N2 neutrophils exhibiting low NETs expression experienced improved PFS (17.3 vs 9.2 months, P=0.008) and OS (40.5 vs 18.3 months, P<0.001) compared with that exhibiting high NETs expression. We also found that tumour-associated N2 neutrophil expressing NETs was negatively associated with CD8+ T cell infiltration, but positively associated with Treg cell infiltration. Conclusion: Tumour-associated N2 neutrophils in NSCLC tissues are the primary cells releasing NETs, and tumour-associated N2 neutrophils with high NETs expression are associated with an immunosuppressive tumour microenvironment, which will impact the efficacy of first-line immunotherapy in NSCLC patients.
Keywords: NETs, neutrophil extracellular traps, NSCLC, Non-small cell lung cancer, TANs, Tumour-associated neutrophils, PFS, Progression-free survival
Received: 16 Sep 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Hong, Ye, Chen, Chai, Yin, Li, Fang, Qian, Yu, Qin, Yao, Zhou, Luo, Shu, Chen, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yong Wang
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