Huang Shiyun, Shi Jiahao, Shen Jianfeng, Fan Xianqun
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, China.
Cancer Lett. 2025 Mar 1;612:217466. doi: 10.1016/j.canlet.2025.217466. Epub 2025 Jan 23.
Neutrophils are pivotal in the immune system and have been recognized as significant contributors to cancer development and progression. These cells undergo metabolic reprogramming in response to various stimulus, including infections, diseases, and the tumor microenvironment (TME). Under normal conditions, neutrophils primarily rely on aerobic glucose metabolism for energy production. However, within the TME featured by hypoxic and nutrient-deprived conditions, they shift to altered anaerobic glycolysis, lipid metabolism, mitochondrial metabolism and amino acid metabolism to perform their immunosuppressive functions and facilitate tumor progression. Targeting neutrophils within the TME is a promising therapeutic approach. Yet, focusing on their metabolic pathways presents a novel strategy to enhance cancer immunotherapy. This review synthesizes the current understanding of neutrophil metabolic reprogramming in the TME, with an emphasis on the underlying molecular mechanisms and signaling pathways. Studying neutrophil metabolism in the TME poses challenges, such as their short lifespan and the metabolic complexity of the environment, necessitating the development of advanced research methodologies. This review also discusses emerging solutions to these challenges. In conclusion, given their integral role in the TME, targeting the metabolic pathways of neutrophils could offer a promising avenue for cancer therapy.
中性粒细胞在免疫系统中起着关键作用，并且已被认为是癌症发生和发展的重要促成因素。这些细胞会响应各种刺激（包括感染、疾病和肿瘤微环境（TME））而发生代谢重编程。在正常情况下，中性粒细胞主要依靠有氧糖代谢来产生能量。然而，在以缺氧和营养缺乏为特征的肿瘤微环境中，它们会转向改变的无氧糖酵解、脂质代谢、线粒体代谢和氨基酸代谢，以发挥其免疫抑制功能并促进肿瘤进展。针对肿瘤微环境中的中性粒细胞是一种很有前景的治疗方法。然而，关注它们的代谢途径提出了一种增强癌症免疫治疗的新策略。本综述综合了目前对肿瘤微环境中中性粒细胞代谢重编程的理解，重点关注其潜在的分子机制和信号通路。研究肿瘤微环境中的中性粒细胞代谢存在挑战，例如它们的寿命较短以及环境的代谢复杂性，因此需要开发先进的研究方法。本综述还讨论了应对这些挑战的新解决方案。总之，鉴于它们在肿瘤微环境中的不可或缺的作用，针对中性粒细胞的代谢途径可能为癌症治疗提供一条有前景的途径。
