这篇研究论文主要探讨了T细胞衰竭（Tex细胞）的潜在分子机制，这是一种在慢性感染和癌症中出现的T细胞功能障碍状态。研究人员通过分析衰竭T细胞的蛋白质组，发现了一种独特的蛋白毒性应激反应（Tex-PSR），其特点是翻译活动增加、伴侣蛋白上调和蛋白质聚集，这与典型的细胞应激反应有所不同。该研究建立了持续的AKT信号传导是驱动Tex-PSR和T细胞衰竭的机制性因素，并通过实验证明仅引入错误折叠的蛋白质就能导致T细胞衰竭。最终，文章指出靶向Tex-PSR相关伴侣蛋白可改善癌症免疫治疗效果，提示Tex-PSR是癌症免疫治疗的新靶点。References: Wang Y, Ma A, Song N J, et al. Proteotoxic stress response drives T cell exhaustion and immune evasion[J]. Nature, 2025: 1-11.
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