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Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing
Cell ( IF 45.5 ) Pub Date : 2017-06-15 00:00:00 , DOI: 10.1016/j.cell.2017.05.035
Chunhong Zheng , Liangtao Zheng , Jae-Kwang Yoo , Huahu Guo , Yuanyuan Zhang , Xinyi Guo , Boxi Kang , Ruozhen Hu , Julie Y. Huang , Qiming Zhang , Zhouzerui Liu , Minghui Dong , Xueda Hu , Wenjun Ouyang , Jirun Peng , Zemin Zhang

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.

中文翻译:

单细胞测序揭示了肝癌中浸润性T细胞的景观

肿瘤浸润淋巴细胞的系统性询问是免疫疗法发展以及预测其在癌症中临床反应的关键。在这里,我们对从六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细胞进行了深层单细胞RNA测序。这些单个细胞的转录概况,再加上组装的T细胞受体(TCR)序列,使我们能够根据其分子和功能特性鉴定11个T细胞亚群,并描绘出它们的发育轨迹。在肝细胞癌(HCC)中,特定的子集(如疲惫的CD8 + T细胞和Tregs)被优先富集并可能在克隆中扩增,我们为每个子集鉴定了特征基因。基因之一,莱利林,在激活的CD8 + T细胞和Tregs上调,并在体外抑制CD8 + T细胞的功能。这份转录组数据汇编为了解癌症的免疫状况提供了宝贵的见识和丰富的资源。
更新日期:2017-06-16
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