肿瘤细胞治疗研究
英文原题：Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.
抗肿瘤免疫的疗效与细胞毒性T细胞的代谢状态相关，而后者对肿瘤微环境敏感。
抗肿瘤免疫的疗效与细胞毒性T细胞的代谢状态相关，而后者对肿瘤微环境敏感。离子信号是否影响适应性抗肿瘤免疫应答尚不清楚。在本研究中，我们表明乳腺癌患者实体瘤中存在钠的富集。氯化钠（NaCl）增强人CD8+ T细胞的活化状态和效应功能，这与代谢适应性的增强相关。这些NaCl诱导的效应转化为体外和体内肿瘤细胞杀伤的增加。在机制上，NaCl诱导的CD8+ T细胞变化与钠诱导的Na+/K+-ATPase活性上调相关，随后是膜超极化，这放大了T细胞受体（TCR）诱导的钙内流和下游TCR信号传导的电动势。因此，我们提出NaCl是急性抗肿瘤免疫的正向调节因子，可能被调控用于治疗性T细胞（如CAR T细胞）的体外预处理。
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.
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