肿瘤微环境代谢重编程调控耗竭性CD8+T细胞研究进展
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1.中山大学孙逸仙纪念医院;2.汕头市中心医院乳腺疾病诊疗中心

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Targeting metabolic reprogramming of tumor microenvironment to reinvigorate exhausted CD8+ T cells and immunotherapy
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1.Sun-yat sen memory hospital;2.4Diagnosis and Treatment Center of Breast Diseases, Shantou Affiliated Hospital, Sun Yat-sen University

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    摘要:

    CD8+T细胞耗竭是免疫疗法低应答率的重要原因之一,而在肿瘤微环境中肿瘤细胞和T细胞之间的“代谢竞争”,造成的缺氧、营养物质的消耗以及代谢废物的产生等,会抑制T细胞代谢并影响其分化,可能对T细胞耗竭的产生有一定影响。了解功能受损的耗竭性T细胞其代谢改变,以及在肿瘤微环境中代谢交互作用和代谢可塑性等,通过调节CD8+耗竭T细胞的代谢,将代谢干预与免疫治疗相结合,恢复T细胞的抗肿瘤活性是肿瘤免疫治疗的重要策略之一。因此,本文对CD8+耗竭性T细胞其代谢特征以及在肿瘤微环境中异常代谢紊乱对T细胞耗竭功能影响和靶向治疗等作一综述。

    Abstract:

    CD8+T cell exhaustion is one of the most important reasons for the low response rate of immunotherapy, yet the "metabolic competition" between tumor cells and T cells in the tumor microenvironment(TME),which causes hypoxia, consumption of nutrients, and accumulation of waste products and so on, can alter or prevent T cell differentiation and may have some impact on the production of exhausted T cells. Understanding the metabolic changes of exhausted T cells with impaired function, as well as the metabolic interactions and plasticity in the TME, implicated that alteration of the metabolic state as a means to reverse CD8+T cell exhaustion and restore their anti-tumor activity.Thus,in this review,we would like to focus on the metabolic characteristics of CD8+ exhausted T cells and how the TME imposes barriers to the metabolism and activity of tumor infiltrating lymphocytes.

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  • 收稿日期:2022-04-25
  • 最后修改日期:2022-04-25
  • 录用日期:2022-05-07
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