瘤MHC I类受限抗原与肠球菌之间的交叉反应
Aurélie Fluckiger1,2, Romain Daillère1,2,3, Mohamed Sassi4
1Gustave Roussy Cancer Campus (GRCC), Villejuif, France.
概括
肠道细菌可以训练免疫细胞对抗癌症. 发现一种特定的细菌蛋白 (TMP) 触发了抗瘤反应,改善了小鼠的癌症免疫疗法,与患者的治疗成功相关.
科学领域:
- 免疫学
- 微生物学
- 癌症学
背景情况:
- 肠道微生物群可能诱导与瘤抗原交叉反应的T细胞.
- 可以利用微生物成分来加强癌症免疫疗法.
研究的目的:
- 调查微生物表位是否可以引起抗瘤T细胞反应.
- 确定特定细菌蛋白在癌症免疫疗法的作用.
主要方法:
- 在Enterococcus hirae的尾部长度测量带蛋白 (TMP) 中发现的MHC I类结合表位.
- 向接受免疫治疗的小鼠注射表达TMP表位的工程细菌菌株.
- 在小鼠中分析了TMP特异性的CD8+T细胞反应.
- 与癌症患者免疫治疗结果相关的肠球菌预兆存在和TMP交叉反应抗原表达.
主要成果:
- 在接受免疫治疗后,携带该导体的小鼠表现出TMP特异性的CD8+ T细胞反应.
- 在小鼠中,表达TMP表位体的工程细菌增强了免疫治疗结果.
- 在癌和肺癌患者中,肠球菌预兆和TMP交叉反应性瘤抗原与PD- 1阻断治疗的长期益处相关.
- 在黑色素瘤患者中检测到与微生物交叉反应的T细胞克隆.
结论:
- 比如TMP,可以引起抗瘤CD8+T细胞的反应.
- 工程细菌表达微生物表位可以改善癌症免疫疗法.
- 特定微生物抗原的存在及其与瘤抗原的交叉反应是预测免疫治疗反应的生物标志物.
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