在癌症中T细胞耗尽的表观遗传调节
Tae Gun Kang1, Jordan T Johnson1,2, Caitlin C Zebley1,2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature reviews. Cancer
|October 28, 2025
概括
T细胞耗尽限制了癌症免疫疗法的有效性. 了解转录和表观遗传控制可以指导下一代的策略,以改善患者的反应和对癌症复发的持久保护.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 癌症免疫疗法,如免疫检查点阻断 (ICB) 和仿真抗原受体 (CAR) T 细胞,已经改变了癌症治疗.
- 然而,大量患者对这些疗法没有反应或出现疾病复发,这表明需要改进策略.
- 抑制T细胞功能和增殖的状态,即T细胞疲劳,是各种癌症中有效的癌症免疫治疗的关键障碍.
研究的目的:
- 在癌症免疫治疗的背景下,审查调节T细胞耗尽的转录和表观遗传机制.
- 阐明T细胞子集特定基因调控程序如何导致免疫疗法失败.
- 提出新的策略,以提高基于T细胞的癌症免疫疗法的临床疗效和耐用性.
主要方法:
- 文献综述侧重于T细胞耗尽的转录和表观遗传调节.
- 分析不同T细胞子集中的基因调控程序.
- 综合当前的知识,以告知未来的治疗发展.
主要成果:
- T 细胞耗尽是限制当前免疫疗法的成功的一个关键机制.
- 转录和表观遗传因素在建立和维持耗尽的T细胞表型方面发挥着至关重要的作用.
- 在T细胞子集中的特定基因调控程序决定了对免疫治疗的反应.
结论:
- 准转录和表观遗传通路为克服T细胞枯竭提供了一个有希望的途径.
- 开发下一代调节这些机制的T细胞免疫疗法可以改善患者的治疗结果.
- 需要加强策略,以增加基于T细胞的癌症治疗的范围,疗效和耐久性.
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