在CAR-T细胞疗法中氧化应激:机制性见解和氧化还原向干预措施
Shichu Xu1, Jiayi Li1, Wenying Li1
1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Critical reviews in oncology/hematology
|December 3, 2025
概括
化学抗原受体 (CAR) T细胞疗法在固体瘤中面临挑战,原因是瘤微环境 (TME) 中的活性氧物种 (ROS). 减轻氧化应激的策略对于提高CAR T细胞对固体瘤的疗效至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 化学抗原受体 (CAR) T细胞疗法在血液癌症中表现有前途,但在固体瘤中扎.
- 固体瘤中的瘤微环境 (TME) 是免疫抑制的,富含活性氧物种 (ROS).
- 较高的ROS水平会损害CAR-T细胞,损害它们的抗瘤功能,并与其他免疫抑制因素协同作用.
研究的目的:
- 审查氧化应激破坏固体瘤中CAR T细胞治疗的机制.
- 突出用于改善CAR T细胞治疗结果的氧化还原向干预措施.
- 为优化治疗策略提供见解,同时保持ROS平衡.
主要方法:
- 关于CAR T细胞治疗,氧化应激和瘤微环境的综合文献综述.
- 在固体瘤中分析了将ROS与CAR T细胞功能障碍联系在一起的机制.
- 评估当前和新兴的氧化还原向干预措施.
主要成果:
- 在TME中,氧化应激会导致DNA损伤,线粒体功能障碍和CAR T细胞的信号改变.
- ROS会加剧TME内的免疫抑制,进一步阻碍CAR T细胞活动.
- 目前正在探索各种策略,包括基因工程,代谢重编程和ROS清理,以克服这些挑战.
结论:
- 氧化应激是CAR T细胞治疗在固体瘤中的有效性的主要障碍.
- 准氧化还原通路提供了一种有前途的方法来增强CAR T细胞功能.
- 对氧化还原向干预的进一步研究对于优化对固体瘤的CAR T细胞治疗至关重要.
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