Abstract：
T cells suffer from long-term antigen stimulation and insufficient energy supply, leading to a decline in their effector functions, memory capabilities, and proliferative capacity, ultimately resulting in T cell exhaustion and an inability to perform normal immune functions in the tumor microenvironment. Therefore, exploring how to restore these exhausted T cells to a state with effector functions is of great significance. Exhausted T cells exhibit a spectrum of molecular alterations, such as heightened expression of inhibitory receptors, shifts in transcription factor profiles, and modifications across epigenetic, metabolic, and transcriptional landscapes. This review provides a comprehensive overview of various strategies to reverse T cell exhaustion, including immune checkpoint blockade, and explores the potential synergistic effects of combining multiple approaches to reverse T cell exhaustion. It offers new insights and methods for achieving more durable and effective reversal of T cell exhaustion.
摘要：
T细胞长期受到抗原刺激,能量供应不足,导致它们的效应器功能下降，记忆能力，和增殖能力，最终导致T细胞耗尽和无法在肿瘤微环境中执行正常的免疫功能。因此,探索如何将这些耗尽的T细胞恢复到具有效应子功能的状态具有重要意义。耗尽的T细胞表现出一系列分子改变，例如抑制受体的表达增强，转录因子谱的变化，以及表观遗传上的修饰，新陈代谢，和转录景观。这篇综述全面概述了逆转T细胞衰竭的各种策略，包括免疫检查点封锁，并探讨了联合多种方法逆转T细胞耗竭的潜在协同作用。它为实现更持久和有效的T细胞衰竭逆转提供了新的见解和方法。
