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癌症背景下的中性粒细胞代谢

Neutrophil metabolism in the cancer context.

作者信息

Bodac Anita, Meylan Etienne

机构信息

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland.

Lung Cancer & Immuno-Oncology Laboratory, Bordet Cancer Research Laboratories, Institut Jules Bordet, Faculty of Medicine, Université Libre de Bruxelles, 1070, Anderlecht, Belgium; Laboratory of Immunobiology, Faculty of Sciences, Université Libre de Bruxelles, 6041, Gosselies, Belgium; ULB Cancer Research Center (U-CRC) and ULB Center for Research in Immunology (U-CRI), Belgium.

出版信息

Semin Immunol. 2021 Oct;57:101583. doi: 10.1016/j.smim.2021.101583. Epub 2021 Dec 25.

Abstract

Neutrophils are critical innate immune cells for the host anti-bacterial defense. Throughout their lifecycle, neutrophils are exposed to different microenvironments and modulate their metabolism to survive and sustain their functions. Although tumor cell metabolism has been intensively investigated, how neutrophil metabolism is affected in cancer remains largely to be discovered. Neutrophils are described as mainly glycolytic cells. However, distinct tumor-associated neutrophil (TAN) states may co-exist in tumors and adapt their metabolism to exert different or even opposing activities ranging from tumor cell killing to tumor support. In this review, we gather evidence about the metabolic mechanisms that underly TANs' pro- or anti-tumoral functions in cancer. We first discuss how tumor-secreted factors and the heterogenous tumor microenvironment can have a strong impact on TAN metabolism. We then describe alternative metabolic pathways used by TANs to exert their functions in cancer, from basic glycolysis to more recently-recognized but less understood metabolic shifts toward mitochondrial oxidative metabolism, lipid and amino acid metabolism and even autophagy. Last, we discuss promising strategies targeting neutrophil metabolism to combat cancer.

摘要

中性粒细胞是宿主抗菌防御中至关重要的固有免疫细胞。在其整个生命周期中,中性粒细胞会暴露于不同的微环境中,并调节自身代谢以存活并维持其功能。尽管肿瘤细胞代谢已得到深入研究,但癌症中中性粒细胞代谢如何受到影响在很大程度上仍有待发现。中性粒细胞被描述为主要进行糖酵解的细胞。然而,不同的肿瘤相关中性粒细胞(TAN)状态可能在肿瘤中共存,并调整其代谢以发挥从杀伤肿瘤细胞到支持肿瘤等不同甚至相反的作用。在本综述中,我们收集了有关TANs在癌症中发挥促肿瘤或抗肿瘤功能的代谢机制的证据。我们首先讨论肿瘤分泌因子和异质性肿瘤微环境如何对TAN代谢产生强烈影响。然后,我们描述TANs在癌症中发挥功能所使用的替代代谢途径,从基本的糖酵解到最近才被认识但了解较少的向线粒体氧化代谢、脂质和氨基酸代谢甚至自噬的代谢转变。最后,我们讨论针对中性粒细胞代谢来对抗癌症的有前景的策略。

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