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氯化钠增强T细胞代谢适应性和细胞毒性
作者:小柯机器人 发布时间:2024/8/29 18:20:57

德国Hans Knöll研究所Christina E. Zielinski团队研究发现,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。2024年8月28日,国际知名学术期刊《自然—免疫学》发表了这一成果。

在本研究中,该研究团队发现乳腺癌患者的实体瘤中存在钠的富集。氯化钠(NaCl)增强了人CD8+T细胞的激活状态和效应功能,这与增强代谢适应性有关。这些NaCl诱导的效应转化为体外和体内增加的肿瘤细胞杀伤。

在机制上,NaCl诱导的CD8+ T细胞的变化与钠诱导的Na+/K+-ATP酶活性上调有关,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,提出NaCl是急性抗肿瘤免疫的阳性调节因子,可能被调节用于治疗性T细胞(如CAR-T细胞)的体外调节。

据了解,抗肿瘤免疫的效果与细胞毒性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。

附:英文原文

Title: Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity

Author: Soll, Dominik, Chu, Chang-Feng, Sun, Shan, Lutz, Veronika, Arunkumar, Mahima, Gachechiladze, Mariam, Schuble, Sascha, Alissa-Alkhalaf, Maha, Nguyen, Trang, Khalil, Michelle-Amirah, Garcia-Ribelles, Ignacio, Mueller, Michael, Buder, Katrin, Michalke, Bernhard, Panagiotou, Gianni, Ziegler-Martin, Kai, Benz, Pascal, Schatzlmaier, Philipp, Hiller, Karsten, Stockinger, Hannes, Luu, Maik, Schober, Kilian, Moosmann, Carolin, Schamel, Wolfgang W., Huber, Magdalena, Zielinski, Christina E.

Issue&Volume: 2024-08-28

Abstract: 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.

DOI: 10.1038/s41590-024-01918-6

Source: https://www.nature.com/articles/s41590-024-01918-6

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex