Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing
Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing
复制标题
单细胞测序揭示肝癌中浸润性 T 细胞的情况
DOI：
10.1016/j.cell.2017.05.035
复制
发表时间：
2017-06-15
期刊：
影响因子：
64.5
通讯作者：
Zhang, Zemin
中科院分区：
文献类型：
--
作者：
Zheng, Chunhong;Zheng, Liangtao;Zhang, Zemin
对肿瘤浸润淋巴细胞的系统研究是免疫疗法开发和预测其在癌症中的临床反应的关键。在这里，我们对从 6 名肝细胞癌患者的外周血、肿瘤和邻近正常组织中分离出的 5,063 个单 T 细胞进行了深度单细胞 RNA 测序。这些单个细胞的转录谱与组装的 T 细胞受体 (TCR) 序列相结合，使我们能够根据其分子和功能特性识别 11 个 T 细胞亚群，并描绘它们的发育轨迹。特定亚群（例如耗尽的 CD8+ T 细胞和 Tregs）在肝细胞癌（HCC）中优先富集并可能克隆扩增，并且我们鉴定了每个亚群的特征基因。其中一种基因，layilin，在激活的 CD8(+) T 细胞和 Tregs 上表达上调，并在体外抑制 CD8(+) T 细胞功能。这份转录组数据概要为了解癌症的免疫状况提供了宝贵的见解和丰富的资源。
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8(+) T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8(+) T cells and Tregs and represses the CD8(+) T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers.