从死亡的癌细胞中释放的无细胞色素颗粒激活了人体淋巴细胞中的免疫检查点:对癌症治疗的含义
Snehal Shabrish1,2, Kavita Pal1,2, Naveen Kumar Khare1,2
1Translational Research Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, India.
来自癌症患者的无细胞色素颗粒 (cfChPs) 激活了淋巴细胞中的PD-1和CTLA-4等免疫检查点. 禁用cfChP可能会提供一种新的癌症免疫治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 免疫检查点封锁是癌症治疗的重大进展.
- 激活免疫检查点的机制在很大程度上是未知的.
- 以前的研究表明,来自癌症患者的无细胞染色素颗粒 (cfChPs) 可以被健康细胞内化,引起生物效应.
研究的目的:
- 研究cfChP在免疫检查点激活中的作用.
- 探索针对癌症免疫治疗的cfChPs的潜在治疗策略.
主要方法:
- 用从癌症患者血清中分离出来的cfChPs治疗人类淋巴细胞.
- 在体内验证使用注射cfChPs的小鼠囊细胞.
- 淋巴细胞暴露于含有来自死亡HeLa细胞的cfChPs的条件介质.
- 免疫检查点表达的评估 (PD-1,CTLA-4,LAG-3,NKG2A,TIM-3). 免疫检查点表达的评估.
- 测试cfChP禁用剂以降低免疫检查点激活的调节.
主要成果:
- cfChPs显著激活了人体淋巴细胞上的多个免疫检查点 (PD-1,CTLA-4,LAG-3,NKG2A,TIM-3).
- 类似的免疫检查点上调被观察到 in vivo 在小鼠脊髓细胞中.
- 缺氧诱导的cfChPs也激活了孤立淋巴细胞中的免疫检查点.
- 使用cfChPs禁用剂的预治疗成功降低了免疫检查点的激活.
结论:
- 来自癌症患者的循环cfChP可以直接激活淋巴细胞上的免疫检查点.
- cfChPs代表了癌症中免疫逃避的新机制.
- 用去活化剂向cfChP,为癌症免疫疗法提供了一个有希望的新途径.
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