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适应性免疫抵抗从发病的干细胞中产生
Yuxuan Miao1, Hanseul Yang1, John Levorse1
1Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Cell
|April 30, 2019
概括
瘤发起干细胞 (tSCs) 通过表达抑制T细胞的CD80来抵抗免疫治疗. 阻止这种相互作用或向TGF-β可以减少癌症免疫治疗后的瘤复发.
科学领域:
- 免疫学
- 癌症学
- 干细胞生物学
背景情况:
- 免疫系统通常会消灭癌细胞.
- 瘤发起干细胞 (tSC) 逃避免疫监测,但机制尚不清楚.
- 了解tSC免疫规避对于有效的癌症免疫治疗至关重要.
研究的目的:
- 研究瘤发起干细胞 (tSCs) 如何抵抗免疫治疗.
- 确定TSC克服免疫监控的机制.
- 开发改善采用细胞转移 (ACT) 免疫疗法的策略.
主要方法:
- 开发了一种用于ACT免疫治疗的皮肤状细胞癌 (SCC) 模型.
- 使用单细胞RNA测序 (RNA-seq) 和谱系追踪.
- 研究了转化生长因子β (TGF-β) 和CD80在tSC免疫逃避中的作用.
主要成果:
- 发现TGF-β反应的tSCs可以抵抗ACT并驱动瘤复发.
- 通过CTLA4抑制细胞毒性T细胞活动的配体CD80.
- 阻断CTLA4或TGF-β,或消去CD80,使tSC对ACT敏感,并减少复发.
结论:
- tSCs利用CD80来积极抑制抗瘤T细胞的反应.
- 免疫检查点通路由tSCs激活以促进免疫逃避.
- 针对tSC介导的免疫抑制提供了一个有前途的策略来提高免疫治疗结果.
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