CD8 T细胞控制肿瘤，但不可避免地在肿瘤微环境中变得功能失调。在这里，我们证明氯化钠 (NaCl) 可以抵消 T 细胞功能障碍，从而促进癌症消退。 CD8 T细胞培养过程中补充氯化钠可诱导效应细胞分化、IFN-γ产生和细胞毒性，同时维持负责干细胞可塑性的基因网络。因此，肿瘤特异性T细胞的过继转移在人源化小鼠模型中产生了优异的抗肿瘤免疫力。在小鼠中，高盐饮食通过抑制终末分化和增强 CD8 T 细胞的效应效力，以 CD8 T 细胞依赖性方式减少实验肿瘤的生长。从机制上讲，氯化钠会增加谷氨酰胺的消耗，这对于转录、表观遗传和功能重编程至关重要。在人类中，CD8 T细胞在肿瘤中进行抗原识别并预测对检查点阻断免疫疗法的有利反应，类似于氯化钠诱导的反应。因此，氯化钠代谢是 CD8 T 细胞效应功能的调节剂，对癌症免疫治疗具有潜在影响。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

CD8+ T cells control tumors but inevitably become dysfunctional in the tumor microenvironment. Here, we show that sodium chloride (NaCl) counteracts T cell dysfunction to promote cancer regression. NaCl supplementation during CD8+ T cell culture induced effector differentiation, IFN-γ production and cytotoxicity while maintaining the gene networks responsible for stem-like plasticity. Accordingly, adoptive transfer of tumor-specific T cells resulted in superior anti-tumor immunity in a humanized mouse model. In mice, a high-salt diet reduced the growth of experimental tumors in a CD8+ T cell-dependent manner by inhibiting terminal differentiation and enhancing the effector potency of CD8+ T cells. Mechanistically, NaCl enhanced glutamine consumption, which was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+ T cells undergoing antigen recognition in tumors and predicting favorable responses to checkpoint blockade immunotherapy resembled those induced by NaCl. Thus, NaCl metabolism is a regulator of CD8+ T cell effector function, with potential implications for cancer immunotherapy.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.