上海交通大学医学院邹强/刘俊岭/苏冰课题组，发现了酰基甘油激酶（AGK）可维持CD8⁺T细胞的代谢状态和免疫反应。 2019年8月，国际学术期刊《细胞—代谢》发表了这一成果。

该课题组研究人员发现，AGK在建立和维持CD8⁺T细胞的代谢和抗肿瘤功能中是必不可少的。AGK缺乏会抑制CD8⁺T细胞体内抗肿瘤和体外增殖的功能。磷脂酰肌醇-3-羟基激酶（PI3K）-哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的激活可增强CD8⁺T细胞的糖酵解水平，且与AGK激酶活性密切相关。作用机制上，T细胞受体（TCR）和CD28刺激PTEN在细胞质膜处聚集，促进了AGK-PTEN结合及AGK介导的PTEN磷酸化，从而限制了PTEN磷酸酶在CD8⁺T细胞中的活性。这些结果表明，AGK通过抑制PTEN活性维持CD8⁺T细胞的代谢和抗肿瘤功能。

据悉，CD8⁺T细胞的扩增和功能发挥依赖于糖酵解途径，但CD8⁺T细胞糖酵解代谢的机制仍不清楚。

FC碰碰胡老虎机法典-提高赢钱机率的下注技巧阅读：

研究人员介绍，该项研究不仅揭示了CD8+ T细胞内部PTEN沉默机制，而且首次阐述了酰基甘油激酶AGK介导肿瘤免疫应答的糖代谢机制，提示了靶向增强AGK活性可能有效增强CD8+ T细胞抗肿瘤功能，为提高肿瘤免疫监测点单抗疗效提供新的策略。（据上海交通大学医学院上海市免疫学研究所）

附：英文原文

Title: Acylglycerol Kinase Maintains Metabolic State and Immune Responses of CD8+ T Cells

Author: Zhilin Hu, Guojun Qu, Xiaoyan Yu, Haojie Jiang, Xiao-Lu Teng, Lei Ding, Qianwen Hu, Xinwei Guo, Yan Zhou, Feng Wang, Hua-Bing Li, Lei Chen, Jin Jiang, Bing Su, Junling Liu, Qiang Zou

Issue&Volume:Volume 30 Issue 2 

Abstract: CD8 + T cell expansions and functions rely on glycolysis, but the mechanisms underlying CD8 + T cell glycolytic metabolism remain elusive. Here, we show that acylglycerol kinase (AGK) is required for the establishment and maintenance of CD8 + T cell metabolic and functional fitness. AGK deficiency dampens CD8 + T cell antitumor functions in vivo and perturbs CD8 + T cell proliferation in vitro. Activation of phosphatidylinositol-3-OH kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, which mediates elevated CD8 + T cell glycolysis, is tightly dependent on AGK kinase activity. Mechanistically, T cell antigen receptor (TCR)- and CD28-stimulated recruitment of PTEN to the plasma membrane facilitates AGK-PTEN interaction and AGK-triggered PTEN phosphorylation, thereby restricting PTEN phosphatase activity in CD8 + T cells. Collectively, these results demonstrate that AGK maintains CD8 + T cell metabolic and functional state by restraining PTEN activity and highlight a critical role for AGK in CD8 + T cell metabolic programming and effector function.

DOI: https://doi.org/10.1016/j.cmet.2019.05.016

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30256-6