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肿瘤微环境中的糖酵解作为改善癌症免疫治疗的靶点。

Glycolysis in tumor microenvironment as a target to improve cancer immunotherapy.

作者信息

Xiao Chu, Tian He, Zheng Yujia, Yang Zhenlin, Li Shuofeng, Fan Tao, Xu Jiachen, Bai Guangyu, Liu Jingjing, Deng Ziqin, Li Chunxiang, He Jie

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

出版信息

Front Cell Dev Biol. 2022 Sep 19;10:1013885. doi: 10.3389/fcell.2022.1013885. eCollection 2022.

Abstract

Cancer cells and immune cells all undergo remarkably metabolic reprogramming during the oncogenesis and tumor immunogenic killing processes. The increased dependency on glycolysis is the most typical trait, profoundly involved in the tumor immune microenvironment and cancer immunity regulation. However, how to best utilize glycolytic targets to boost anti-tumor immunity and improve immunotherapies are not fully illustrated. In this review, we describe the glycolytic remodeling of various immune cells within the tumor microenvironment (TME) and the deleterious effects of limited nutrients and acidification derived from enhanced tumor glycolysis on immunological anti-tumor capacity. Moreover, we elucidate the underlying regulatory mechanisms of glycolytic reprogramming, including the crosstalk between metabolic pathways and immune checkpoint signaling. Importantly, we summarize the potential glycolysis-related targets that are expected to improve immunotherapy benefits. Our understanding of metabolic effects on anti-tumor immunity will be instrumental for future therapeutic regimen development.

摘要

癌细胞和免疫细胞在肿瘤发生和肿瘤免疫杀伤过程中均经历显著的代谢重编程。对糖酵解依赖性的增加是最典型的特征,其与肿瘤免疫微环境和癌症免疫调节密切相关。然而,如何最佳利用糖酵解靶点来增强抗肿瘤免疫力并改善免疫疗法尚未得到充分阐明。在本综述中,我们描述了肿瘤微环境(TME)中各种免疫细胞的糖酵解重塑,以及肿瘤糖酵解增强导致的营养物质有限和酸化对免疫抗肿瘤能力的有害影响。此外,我们阐明了糖酵解重编程的潜在调控机制,包括代谢途径与免疫检查点信号之间的相互作用。重要的是,我们总结了有望改善免疫治疗效果的潜在糖酵解相关靶点。我们对代谢对抗肿瘤免疫影响的理解将有助于未来治疗方案的制定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f46/9527271/2e393e4f738a/fcell-10-1013885-g001.jpg

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