一个微生物调节的检查点将免疫抑制性肠道T细胞引入癌症
Marine Fidelle1,2,3, Conrad Rauber1,2,3,4, Carolina Alves Costa Silva1,2,3
1Gustave Roussy Cancer Campus, Villejuif Cedex, France.
Science (New York, N.Y.)
|June 8, 2023
概括
抗生素通过改变肠道细菌来降低癌症免疫疗法的有效性. 这导致MAdCAM-1的丧失,促进T细胞向瘤迁移并抑制免疫反应.
科学领域:
- 免疫学
- 癌症学
- 微生物组研究
背景情况:
- 抗生素 (ABX) 损害了癌症患者的编程细胞死亡蛋白1 (PD-1) 阻断功效.
- 癌症中抗生素诱导免疫抑制的机制尚未完全理解.
研究的目的:
- 阐明抗生素破坏PD-1阻断功能的机制.
- 确定影响癌症免疫监测的与肠道相关的免疫检查点.
主要方法:
- 研究了Enterocloster物种对肠道重新定居的作用.
- 分析了MAdCAM-1/α4β7整体轴及其对调节性T细胞的影响.
- 在临床前模型中使用了口腔检测,遗传缺陷,抗体中和,便微生物群移植和IL-17A中和.
- 肺癌,脏癌和膀癌患者的结局与可溶性MAdCAM-1水平相关.
主要成果:
- 抗生素后的Enterocloster物种降低了MAdCAM-1状细胞的调节,促使体调节性α4β7+CD4+T17细胞迁移到瘤中.
- 口服的Enterocloster,MAdCAM-1缺乏或α4β7整合素中和模仿了这些免疫抑制作用.
- 便微生物移植和IL-17A中和可以抵消抗生素诱导的免疫抑制.
- 在癌症患者中,低血清可溶MAdCAM-1水平与负面预后相关.
结论:
- MAdCAM-1-α4β7轴是抗生素诱导的癌症免疫抑制的一个关键介质.
- 这一轴代表了一个可操作的肠道免疫检查点,用于增强癌症免疫监测和免疫治疗.
- 向肠道微生物群和MAdCAM-1-α4β7通路可能改善癌症治疗结果.
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