肿瘤微环境中的氯化钠增强 T 细胞代谢适应性和细胞毒性。
Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.
发表日期：2024 Aug 28
作者：
Dominik Soll, Chang-Feng Chu, Shan Sun, Veronika Lutz, Mahima Arunkumar, Mariam Gachechiladze, Sascha Schäuble, Maha Alissa-Alkhalaf, Trang Nguyen, Michelle-Amirah Khalil, Ignacio Garcia-Ribelles, Michael Mueller, Katrin Buder, Bernhard Michalke, Gianni Panagiotou, Kai Ziegler-Martin, Pascal Benz, Philipp Schatzlmaier, Karsten Hiller, Hannes Stockinger, Maik Luu, Kilian Schober, Carolin Moosmann, Wolfgang W Schamel, Magdalena Huber, Christina E Zielinski
来源：
NATURE IMMUNOLOGY
摘要：
抗肿瘤免疫的功效与细胞毒性T细胞的代谢状态有关，细胞毒性T细胞对肿瘤微环境敏感。离子信号是否影响适应性抗肿瘤免疫反应尚不清楚。在本研究中，我们发现乳腺癌患者的实体瘤中钠含量较高。氯化钠 (NaCl) 增强人类 CD8 T 细胞的激活状态和效应器功能，这与增强代谢适应性有关。这些 NaCl 诱导的作用转化为体外和体内肿瘤细胞杀伤力的增加。从机制上讲，氯化钠诱导的 CD8 T 细胞变化与钠诱导的 Na /K -ATP 酶活性上调有关，随后发生膜超极化，从而放大了 T 细胞受体 (TCR) 诱导的钙流入和下游 TCR 信号传导的电动势。因此，我们认为 NaCl 是急性抗肿瘤免疫的正调节剂，可对其进行调节以用于治疗性 T 细胞（例如 CAR T 细胞）的离体调节。© 2024。作者。
The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer. Sodium chloride (NaCl) enhances the activation state and effector functions of human CD8+ T cells, which is associated with enhanced metabolic fitness. These NaCl-induced effects translate into increased tumor cell killing in vitro and in vivo. Mechanistically, NaCl-induced changes in CD8+ T cells are linked to sodium-induced upregulation of Na+/K+-ATPase activity, followed by membrane hyperpolarization, which magnifies the electromotive force for T cell receptor (TCR)-induced calcium influx and downstream TCR signaling. We therefore propose that NaCl is a positive regulator of acute antitumor immunity that might be modulated for ex vivo conditioning of therapeutic T cells, such as CAR T cells.© 2024. The Author(s).