PDF(Pubmed)
Abstract：
The fundamental principle of immune checkpoint blockade (ICB) is to protect tumor-infiltrating T cells from being exhausted. Despite the remarkable success achieved by ICB treatment, only a small group of patients benefit from it. Characterized by a hypofunctional state with the expression of multiple inhibitory receptors, exhausted T (Tex) cells are a major obstacle in improving ICB. T cell exhaustion is a progressive process which adapts to persistent antigen stimulation in chronic infections and cancers. In this review, we elucidate the heterogeneity of Tex cells and offer new insights into the hierarchical transcriptional regulation of T cell exhaustion. Factors and signaling pathways that induce and promote exhaustion are also summarized. Moreover, we review the epigenetic and metabolic alterations of Tex cells and discuss how PD-1 signaling affects the balance between T cell activation and exhaustion, aiming to provide more therapeutic targets for applications of combinational immunotherapies.
摘要：
免疫检查点阻断(ICB)的基本原理是保护肿瘤浸润性T细胞不被耗尽。尽管ICB治疗取得了显著的成功，只有一小部分患者从中受益。以多种抑制性受体表达的功能低下状态为特征，耗尽的T(Tex)细胞是改善ICB的主要障碍。T细胞耗竭是一个渐进的过程，适应慢性感染和癌症中持续的抗原刺激。在这次审查中,我们阐明了Tex细胞的异质性，并为T细胞耗竭的分级转录调控提供了新的见解。还总结了诱导和促进耗竭的因素和信号通路。此外，我们回顾了Tex细胞的表观遗传和代谢改变，并讨论了PD-1信号如何影响T细胞活化和耗尽之间的平衡，旨在为联合免疫疗法的应用提供更多的治疗靶点。
