Single-cell RNA-sequencing analyses identify heterogeneity of CD8(+) T cell subpopulations and novel therapy targets in melanoma.
Single-cell RNA-sequencing analyses identify heterogeneity of CD8(+) T cell subpopulations and novel therapy targets in melanoma.
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DOI：
10.1016/j.omto.2020.12.003
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发表时间：
2021-03-26
期刊：
影响因子：
--
通讯作者：
Li R
中科院分区：
文献类型：
--
作者：
Deng W;Ma Y;Su Z;Liu Y;Liang P;Huang C;Liu X;Shao J;Zhang Y;Zhang K;Chen J;Li R
CD 8 + T细胞是建立抗肿瘤免疫的关键，其高浸润性与有利的肿瘤相关。然而，肿瘤微环境中的几种CD 8 + T细胞亚群可能在预后、进展和免疫治疗中发挥不同的作用。在这里，我们分析了先前发表的单细胞RNA测序（scRNA-seq）黑色素瘤数据，以探索CD 8 + T细胞亚群的异质性，并确定了7个主要亚群。我们发现耗竭的CD 8 + T细胞亚群2的高浸润将有助于不利的疾病。相反，大比例的幼稚/记忆细胞和细胞毒性CD 8 + T细胞亚群3将导致有利的免疫应答。值得注意的是，细胞毒性CD 8 + T细胞亚群3的比例将在晚期黑素瘤样品中降低，而耗尽的CD 8 + T细胞亚群2的比例将增加。我们还发现，高异常活动的代谢途径存在于耗尽的CD 8 + T细胞亚群1。值得注意的是，免疫抑制检查点PD-1和CTLA-4信号通路在耗尽的CD 8 + T细胞亚群中上调。此外，本研究还描绘了不同亚群之间免疫检查点的动态转录景观。此外，我们确定了三个过表达的基因（PMEL，TYRP 1和EDNRB），这些基因与不良免疫反应显著相关，并且仅在耗尽的CD 8 + T细胞亚群2中表达。重要的是，与其他肿瘤相比，它们在黑色素瘤样本中的表达最高。总的来说，我们表征了黑色素瘤中的CD 8 + T细胞亚群，并确定了不仅免疫抑制检查点的基因，而且PMEL、TYRP 1和EDNRB也可以作为黑色素瘤治疗的潜在靶点。CD 8 + T细胞对于抗肿瘤免疫至关重要，但不同的细胞亚群具有异质性功能。在这里，邓等人。描述了黑色素瘤中的CD 8 + T细胞亚群，并确定了不仅免疫抑制检查点的基因，而且PMEL、TYRP 1和EDNRB也可以作为黑色素瘤治疗的潜在靶点。
CD8+ T cells are crucial to establish antitumor immunity, and their high infiltration associates with favorable prognoses. However, several CD8+ T cell subpopulations in the tumor microenvironment may play different roles in prognosis, progression, and immunotherapy. Here, we analyzed prior published single-cell RNA-sequencing (scRNA-seq) melanoma data to explore the heterogeneity of CD8+ T cell subpopulations and identified 7 major subpopulations. We found that high infiltration of exhausted CD8+ T cell subpopulation 2 would contribute to unfavorable prognoses. In contrast, a large proportion of naive/memory cells and cytotoxic CD8+ T cell subpopulation 3 would lead to favorable prognoses. Notably, the proportion of the cytotoxic CD8+ T cell subpopulation 3 would decrease in later-stage melanoma samples, while that of the exhausted CD8+ T cell subpopulation 2 would increase. We also found that high abnormal activities of metabolic pathways existed in exhausted CD8+ T cell subpopulation 1. Significantly, immunosuppressive checkpoints PD-1 and CTLA-4 signaling pathways were upregulated in exhausted CD8+ T cell subpopulations. In addition, a dynamic transcript landscape of immune checkpoints among different subpopulations was also depicted in this study. Moreover, we identified three overexpressed genes (PMEL, TYRP1, and EDNRB) that were significantly correlated to poor prognoses and only expressed in exhausted CD8+ T cell subpopulation 2. Importantly, they showed the highest expression in melanoma samples compared to other tumors. In general, we characterized the CD8+ T cell subpopulations in melanoma and identified that not only genes of immunosuppressive checkpoints but also PMEL, TYRP1, and EDNRB could serve as potential targets for melanoma therapy. CD8+ T cells are crucial for antitumor immunity, yet different cell subpopulations have heterogeneous functions. Here, Deng et al. characterized the CD8+ T cell subpopulations in melanoma and identified that not only genes of immunosuppressive checkpoints but also PMEL, TYRP1, and EDNRB could serve as potential targets for melanoma therapy.
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DOI：
10.1186/s13046-016-0475-z
发表时间：
2017-01-23
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
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