肿瘤微环境代谢重编程调控耗竭性CD8+T细胞研究进展

Targeting metabolic reprogramming of tumor microenvironment to reinvigorate exhausted CD8+ T cells and immunotherapy

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.