Ma Mengqing, Hu Rui, Huang Qi, Zhong Xin, Li Jing, Lv Minling, Yi Jinyu, Sun Jialing, Fan Kongli, Xu Youhua, Zhou Xiaozhou
Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macao; Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China; Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China.
Department of Liver Disease, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China; Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China.
Pharmacol Res. 2025 Jul;217:107811. doi: 10.1016/j.phrs.2025.107811. Epub 2025 Jun 2.
Neutrophils are an important component of the tumor microenvironment, with the majority of previous research concentrating on their anti-tumor role. Recent research indicates that elevated neutrophil-lymphocyte ratios are indicative of worse cancer prognoses. In addition, it revealed the functional transition of neutrophils are related with metabolic regulation within the tumor microenvironment.The metabolic-immune axis has emerged as a master regulator of tumor progression, yet the role of neutrophil-centric crosstalk in this paradigm remains enigmatic. Therefore, this study highlights the innovative role of neutrophils in tumorigenesis, particularly the regulatory effect on tumor niche transformation after glucose metabolism reprogramming. Simultaneously, we discussed how the tumor microenvironment alters the glucose metabolism of neutrophils, influences their life cycle, and modifies their localization and activity inside the tumor niche. In addition, targeted neutrophils, including new therapies in clinical trials, offer new possibilities for cancer treatment. This work establishes neutrophil glycolysis as a linchpin of the metabolic-immune ecosystem and provides a combinatorial therapeutic blueprint to dismantle pro-tumorigenic niches.
中性粒细胞是肿瘤微环境的重要组成部分，以往的大多数研究都集中在它们的抗肿瘤作用上。最近的研究表明，中性粒细胞与淋巴细胞比例升高表明癌症预后较差。此外，研究还揭示了中性粒细胞的功能转变与肿瘤微环境中的代谢调节有关。代谢-免疫轴已成为肿瘤进展的主要调节因子，但在这一模式中以中性粒细胞为中心的相互作用的作用仍不清楚。因此，本研究强调了中性粒细胞在肿瘤发生中的创新作用，特别是对葡萄糖代谢重编程后肿瘤微环境转变的调节作用。同时，我们讨论了肿瘤微环境如何改变中性粒细胞的葡萄糖代谢，影响其生命周期，并改变其在肿瘤微环境中的定位和活性。此外，靶向中性粒细胞，包括临床试验中的新疗法，为癌症治疗提供了新的可能性。这项工作将中性粒细胞糖酵解确立为代谢-免疫生态系统的关键，并提供了一个组合治疗蓝图，以消除促肿瘤微环境。
