Nature：李子海团队揭开T细胞耗竭的根本机制——蛋白错误折叠引起的毒性应激反应，为新一代癌症免疫疗法指明方向

Core Insights - The article discusses T cell exhaustion as a critical mechanism in cancer immunotherapy resistance, highlighting the role of a specific stress response called Tex-PSR [3][4][10] Group 1: T Cell Exhaustion Mechanism - T cell exhaustion (Tex) is characterized by reduced effector function and increased expression of inhibitory receptors, driven by persistent antigen exposure and adverse microenvironments [3] - The study identifies a unique stress response, Tex-PSR, which is triggered by the accumulation of misfolded proteins, leading to T cell exhaustion and immune evasion [4][9] Group 2: Research Findings - The research provides a comprehensive protein landscape of Tex cells under various conditions, revealing inconsistencies between mRNA transcription levels and protein expression [7][8] - Tex-PSR is marked by increased global protein synthesis, unlike the classical unfolded protein response (UPR), which typically inhibits protein synthesis [8][13] Group 3: Clinical Implications - The findings suggest that targeting the Tex-PSR pathway could represent a new direction for cancer immunotherapy, potentially improving T cell vitality and reversing exhaustion [10][12] - The study indicates that the Tex-PSR characteristics are also present in exhausted T cells from human cancer patients, correlating with poor clinical responses to immunotherapy [9][10]