Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells
Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells
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DOI：
10.1016/j.celrep.2019.10.131
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发表时间：
2019-12-03
期刊：
影响因子：
8.8
通讯作者：
Bosselut, Remy
中科院分区：
文献类型：
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作者：
Magen, Assaf;Nie, Jia;Bosselut, Remy
目前大多数肿瘤免疫治疗策略都利用细胞毒性 CD8(+) T 细胞。尽管有证据表明 CD8+ 肿瘤浸润淋巴细胞 (TIL) 具有临床潜力，但其功能多样性限制了我们利用其活性的能力。在这里，我们使用单细胞 mRNA 测序来分析肿瘤特异性 CD8(+) TIL 和引流淋巴结 (dLN) T 细胞的反应。表征亚群的计算方法确定了 TIL 转录组模式与急性和慢性抗病毒反应显着不同，并且由表达 T-bet 的 1 型辅助性 T (Th1) 样细胞的多样性主导。相反，dLN 反应包括滤泡辅助 T (Tfh) 细胞，但缺乏 Th1 细胞。我们在 Th1 样 TIL 中发现了 I 型干扰素驱动的特征，并表明它存在于人类癌症中，其中它与检查点治疗的反应呈负相关。我们的研究提供了一种概念验证方法来表征肿瘤特异性 CD8(+) T 细胞效应程序。针对这些计划应该有助于改善免疫治疗策略。
Most current tumor immunotherapy strategies leverage cytotoxic CD8(+) T cells. Despite evidence for clinical potential of CD8(+) tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific CD8(+) TILs and draining lymph node (dLN) T cells. Computational approaches to characterize subpopulations identify TIL transcriptomic patterns strikingly distinct from acute and chronic anti-viral responses and dominated by diversity among T-bet-expressing T helper type 1 (Th1)-like cells. In contrast, the dLN response includes T follicular helper (Tfh) cells but lacks Th1 cells. We identify a type I interferon-driven signature in Th1-like TILs and show that it is found in human cancers, in which it is negatively associated with response to checkpoint therapy. Our study provides a proof-of-concept methodology to characterize tumor-specific CD8(+) T cell effector programs. Targeting these programs should help improve immunotherapy strategies.