CD8^+T细胞耗竭及靶向CD8^+T细胞免疫治疗的研究进展

Progress in researches of CD8^+T cell exhaustion and CD8^+T cellstargeted immunotherapy

T细胞耗竭是慢性感染和肿瘤状态下T细胞发生的一种功能障碍状态。耗竭T细胞效应功能低下,持续高表达抑制性受体,表达转录因子谱与效应和记忆T细胞明显不同。耗竭状态削弱T细胞对感染和肿瘤的有效控制,导致慢性持续感染和肿瘤发生。耗竭T细胞的分化特征、表型标志和功能逆转对临床抗感染和抗肿瘤具有重要的指导意义。靶向耗竭T细胞的免疫治疗已经在实验动物模型和临床治疗研究中获得了较为理想的效果。为此,本文对CD8^+T细胞耗竭特点、影响因素、表型功能与临床治疗等作一综述。

T cell exhaustion is an unusual dysfunctional state of T cells during chronic viral infections andcancer. Exhausted T cells have reduced effector function, consistently and highly express inhibitory receptors, andexpress a distinct transcriptional profile from effector and memory T cells. Exhaustion state will weaken the effectivecontrol of viral copy and tumors, resulted in chronic persistence infection and tumor proliferation. The researchachievements of the differentiation signature, phenotypic markers and reverse function of exhausted T cells play akey guiding role in anti-infection and anti-tumor clinical therapy. Additionally, exhausted T cells-targetedimmunotherapies have obtained quite satisfied achievements in experimental animal models and clinical trials.Thus, this review will focus on the progress of researches in exhausted CD8^＋T cells characteristic, function andimmunotherapy in clinical trials.