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癌症代谢重编程与免疫应答。

The cancer metabolic reprogramming and immune response.

机构信息

Hunan Key Laboratory of Cancer Metabolism, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, 283 Tongzipo Road, 410013, Changsha, Hunan, China.

University of South China, 421001, Hengyang, Hunan, China.

出版信息

Mol Cancer. 2021 Feb 5;20(1):28. doi: 10.1186/s12943-021-01316-8.

Abstract

The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

摘要

癌症和免疫细胞的代谢重编程重叠是肿瘤抗肿瘤免疫反应的一个假定决定因素。越来越多的证据表明,癌症代谢不仅在维持肿瘤发生和存活的癌症信号传导中起着至关重要的作用,而且通过代谢物的释放和影响免疫分子的表达(如乳酸盐、PGE、精氨酸等),对抗肿瘤免疫反应的调节也有更广泛的影响。实际上,肿瘤和免疫细胞之间的这种能量相互作用导致肿瘤生态系统中的代谢竞争,限制营养物质的可用性并导致微环境酸中毒,从而抑制免疫细胞的功能。更有趣的是,各种类型的免疫细胞在维持自身和身体内环境平衡的过程中也需要进行代谢重编程。目前,越来越多的研究指出,免疫细胞在增殖、分化和执行效应功能的过程中会经历代谢重编程,这对于免疫反应是必不可少的。在此,我们讨论了癌细胞和免疫细胞的代谢重编程如何调节抗肿瘤免疫反应,以及在癌症免疫治疗背景下靶向代谢途径的可能方法。我们还描述了免疫治疗和代谢干预之间的假设联合治疗,可用于更好地释放抗癌疗法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a0d/7863491/48be9c999614/12943_2021_1316_Fig1_HTML.jpg

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