Lin Jun, He Xian-Lu, Zhang Wei-Wei, Mo Chun-Fen
Department of General Surgery, Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.
Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China.
Front Cell Dev Biol. 2025 Apr 24;13:1584987. doi: 10.3389/fcell.2025.1584987. eCollection 2025.
Tumor-associated neutrophils (TANs), pivotal immune cells within the tumor microenvironment (TME), exhibit dual potential in both pro- and anti-tumorigenic effects. These cells display remarkable heterogeneity and plasticity within the TME, adapting to hypoxic and nutrient-deprived conditions through metabolic reprogramming while critically influencing tumor progression, metastasis, and immune evasion. The metabolic reprogramming of TANs not only modulates their functional phenotypes but also reshapes tumor biological behaviors and therapeutic responses by regulating metabolic intermediates and cellular interactions within the TME. Therefore, elucidating the mechanisms underlying TANs metabolic reprogramming has significant implications for deciphering the molecular basis of tumorigenesis, identifying novel therapeutic targets, and optimizing immunotherapeutic strategies. This review systematically summarizes current knowledge regarding metabolic reprogramming mechanisms of TANs in the TME and their impact on tumor progression. We particularly focus on: 1) TAN-specific alterations in glucose, lipid, and amino acid metabolism within the TME; 2) Emerging immunotherapeutic strategies targeting TANs metabolic pathways; 3) Recent advances in understanding TAN-mediated immune evasion and therapy resistance. Furthermore, this review discusses potential challenges and corresponding solutions in targeting TANs metabolic reprogramming for therapeutic intervention, aiming to provide novel insights for advancing cancer immunotherapy.
肿瘤相关中性粒细胞（TANs）是肿瘤微环境（TME）中的关键免疫细胞，在肿瘤发生的促进和抑制作用方面具有双重潜力。这些细胞在TME中表现出显著的异质性和可塑性，通过代谢重编程适应缺氧和营养缺乏的条件，同时对肿瘤进展、转移和免疫逃逸产生关键影响。TANs的代谢重编程不仅调节其功能表型，还通过调节TME内的代谢中间体和细胞相互作用重塑肿瘤生物学行为和治疗反应。因此，阐明TANs代谢重编程的机制对于解读肿瘤发生的分子基础、识别新的治疗靶点以及优化免疫治疗策略具有重要意义。本综述系统地总结了目前关于TME中TANs代谢重编程机制及其对肿瘤进展影响的知识。我们特别关注：1）TME内TANs在葡萄糖、脂质和氨基酸代谢方面的特异性改变；2）针对TANs代谢途径的新兴免疫治疗策略；3）在理解TAN介导的免疫逃逸和治疗抗性方面的最新进展。此外，本综述讨论了针对TANs代谢重编程进行治疗干预的潜在挑战和相应解决方案，旨在为推进癌症免疫治疗提供新的见解。
