血统追踪揭示了T细胞在结直肠癌中的动态关系
Lei Zhang1, Xin Yu2, Liangtao Zheng1
1Beijing Advanced Innovation Centre for Genomics, Peking-Tsinghua Centre for Life Sciences, Peking University, Beijing, China.
Nature
|November 28, 2018
概括
T细胞受体 (TCR) 追踪显示了T细胞的不同子集和它们在结肠直肠癌中的关系. 这种方法有助于了解T细胞动态和癌症免疫治疗中的潜在治疗点.
科学领域:
- 免疫学
- 癌症学
- 基因组学
背景情况:
- T细胞对于癌症免疫疗法至关重要,但它们在瘤中的发育和迁移尚未完全理解.
- 在瘤微环境中,T细胞受体 (TCR) 提供潜在的谱系标签.
研究的目的:
- 使用单细胞RNA测序和TCR追踪量化分析结直肠癌中T细胞子集之间的动态关系.
- 识别不同的T细胞子集,它们的功能,克隆性和瘤中的发育关系.
主要方法:
- 从12名结肠直肠癌患者获得11138个单T细胞的转录组.
- 通过RNA测序和TCR追踪 (STARTRAC) 指数进行单个T细胞分析.
- 在20个已识别的T细胞子集中量化分析了动态关系.
主要成果:
- 通过基于TCR的命运决定,确定了不同的CD8+效应体和"耗尽"的T细胞子集,与瘤中的CD8+效应体记忆细胞联系在一起.
- 在大多数瘤透T调节细胞 (Treg) 中观察到克隆特异性,其中一些Treg克隆与T辅助细胞 (TH) 克隆有关.
- 发现两个IFNG+TH1类细胞群 (GZMK+效应记忆和CXCL13+BHLHE40+TH1类细胞) 与不同的转录因子相关;CXCL13+BHLHE40+细胞在微卫星不稳定的瘤中被丰富,与有利的免疫检查点阻塞反应相关.
结论:
- STARTRAC分析提供了一种全面的方法来剖析结直肠癌中的T细胞特性.
- 这些发现为T细胞动态和结直肠癌和其他恶性瘤的潜在治疗策略提供了洞察力.
- 在微卫星不稳定的瘤中,CXCL13+BHLHE40+TH1样细胞子集可以预测免疫检查点阻塞的反应.
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