Sheervalilou Milad, Ghanei Mostafa, Arabfard Masoud
Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Med Oncol. 2025 Jun 16;42(7):266. doi: 10.1007/s12032-025-02831-0.
Lung cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), remain the leading cause of cancer-related mortality worldwide, with the tumor microenvironment (TME) playing a crucial role in disease progression. Among the immune components of the TME, tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs) have garnered increasing attention due to their complex and sometimes contrasting roles in tumor biology. TANs exhibit both protumor and antitumor functions, either promoting lung cancer progression through enhanced tumor cell proliferation, invasion, angiogenesis, and metastasis or exerting antitumor effects by stimulating immune responses and cytotoxicity. Their impact is largely context-dependent and influenced by interactions with other immune cells, particularly T cells, within the lung cancer TME. Additionally, NETs, secreted by neutrophils, play a pivotal role in tumor progression by facilitating tumor growth, invasion, metastasis, and cancer-associated thrombosis. Although the precise mechanisms underlying NET-mediated tumor promotion are not yet fully elucidated, accumulating evidence suggests their significant contribution to lung cancer pathophysiology. This review synthesizes recent findings on the dual roles of TANs, their interactions with T cells, and the emerging molecular insights into NETs in lung cancer. By elucidating the intricate interplay between TANs, NETs, and immune cells, we aim to provide a foundation for the development of novel therapeutic strategies targeting neutrophil-mediated tumor dynamics.
肺癌，包括小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC），仍然是全球癌症相关死亡的主要原因，肿瘤微环境（TME）在疾病进展中起着关键作用。在TME的免疫成分中，肿瘤相关中性粒细胞（TANs）和中性粒细胞胞外陷阱（NETs）因其在肿瘤生物学中的复杂且有时相互矛盾的作用而受到越来越多的关注。TANs具有促肿瘤和抗肿瘤功能，既可以通过增强肿瘤细胞增殖、侵袭、血管生成和转移来促进肺癌进展，也可以通过刺激免疫反应和细胞毒性发挥抗肿瘤作用。它们的影响在很大程度上取决于背景，并受到与肺癌TME内其他免疫细胞（特别是T细胞）相互作用的影响。此外，中性粒细胞分泌的NETs通过促进肿瘤生长、侵袭、转移和癌症相关血栓形成，在肿瘤进展中起关键作用。尽管NET介导肿瘤促进的确切机制尚未完全阐明，但越来越多的证据表明它们对肺癌病理生理学有重要贡献。本综述综合了关于TANs的双重作用、它们与T细胞的相互作用以及肺癌中NETs的新分子见解的最新发现。通过阐明TANs、NETs和免疫细胞之间的复杂相互作用，我们旨在为开发针对中性粒细胞介导的肿瘤动态的新型治疗策略提供基础。
