多发性骨髓瘤衍生的二氧化硫通过诱导线粒体功能障碍驱动CAR-T细胞耗尽
Zhengyu Yu1, Hua Lin2, Jingran He3
1Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Redox biology
|January 22, 2026
概括
多发性骨髓瘤患者的二氧化硫 (SO2) 积累会损害CAR-T细胞功能,导致疲劳. 准SO2-DRP1通路可能会恢复CAR-T细胞的抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢障碍 代谢障碍 代谢障碍
- 癌症治疗 癌症治疗
背景情况:
- 卡特-T细胞耗尽阻碍了癌症免疫疗法的有效性.
- 内生二氧化硫 (SO2) 调节免疫细胞功能,但其在CAR-T细胞衰竭中的作用尚不清楚.
研究的目的:
- 研究SO2在骨髓微环境中的CAR-T细胞耗尽中的作用.
- 阐明SO2诱导CAR-T细胞功能障碍的分子机制.
主要方法:
- 在复发多发性骨髓瘤患者中分析SO2水平.
- 评估CAR-T细胞透,线粒体功能和细胞因子分泌.
- 涉及胺相关蛋白1 (DRP1) 硫和线粒体裂变的机制研究.
主要成果:
- 在骨髓微环境中积聚的SO2抑制了T细胞的透,并促进了疲劳.
- SO2破坏了CAR-T细胞的线粒体形态和膜潜力,损害了功能.
- SO2通过DRP1 Cys607硫化增强DRP1-VADC1相互作用和线粒体裂变,增加DRP1 GTPase活性.
结论:
- SO2诱导的线粒体功能障碍有助于CAR-T细胞疲劳.
- SO2-DRP1轴是克服CAR-T细胞代谢疲劳和增强抗瘤免疫力的新型治疗点.
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