Feng Ye, Liu Guang, Li Haiqing, Cheng Lin
Shanghai Sunshine Rehabilitation Center (Shanghai YangZhi Rehabilitation Hospital), Tongji University School of Medicine, Shanghai, 201619, China.
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200023, China.
J Hematol Oncol. 2025 Aug 12;18(1):79. doi: 10.1186/s13045-025-01731-0.
Neutrophils have long been regarded as cells of a limited lifespan, known to produce pro-inflammatory molecules, and primarily engaged in combating infections. However, recent advancements in single-cell analysis and molecular biology have revealed their remarkable heterogeneity and plasticity, particularly within the context of tumors. This review explores the development and diversity of neutrophils under both physiological and pathological conditions, with a particular focus on their roles in cancer. The discussion encompasses the emergence of distinct neutrophil subtypes, particularly senescent neutrophils, within tumors and their context-dependent functions in tumorigenesis, progression, metastasis, and recurrence. The plasticity of these cells, driven by intrinsic factors and the tumor microenvironment, allows them to be reprogrammed between pro-tumor and anti-tumor phenotypes. This process is influenced by cytokines, metabolic reprogramming, and interactions with other immune cells. The potential of targeting and engineering neutrophil as a therapeutic avenue for cancer treatment is further underscored, including the use of senolytic agents, metabolic inhibitors, and reprogramming strategies. Finally, future research directions are proposed to further elucidate the mechanisms underlying neutrophil heterogeneity and plasticity, with the aim of developing novel therapeutic approaches to modulate neutrophil function in cancer.
长期以来，中性粒细胞一直被视为寿命有限的细胞，已知其能产生促炎分子，主要参与对抗感染。然而，单细胞分析和分子生物学的最新进展揭示了它们显著的异质性和可塑性，尤其是在肿瘤背景下。本综述探讨了生理和病理条件下中性粒细胞的发育和多样性，特别关注它们在癌症中的作用。讨论内容包括肿瘤内不同中性粒细胞亚型（特别是衰老中性粒细胞）的出现及其在肿瘤发生、进展、转移和复发中依赖于背景的功能。这些细胞的可塑性由内在因素和肿瘤微环境驱动，使它们能够在促肿瘤和抗肿瘤表型之间重新编程。这个过程受到细胞因子、代谢重编程以及与其他免疫细胞相互作用的影响。进一步强调了将靶向和改造中性粒细胞作为癌症治疗途径的潜力，包括使用衰老细胞溶解剂、代谢抑制剂和重编程策略。最后，提出了未来的研究方向，以进一步阐明中性粒细胞异质性和可塑性的潜在机制，旨在开发新的治疗方法来调节癌症中中性粒细胞的功能。
