Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing

被引:1868
作者
Zheng, Chunhong [1 ,2 ]
Zheng, Liangtao [3 ]
Yoo, Jae-Kwang [4 ]
Guo, Huahu [5 ,6 ,7 ]
Zhang, Yuanyuan [1 ,2 ]
Guo, Xinyi [1 ,2 ]
Kang, Boxi [1 ,2 ]
Hu, Ruozhen [4 ]
Huang, Julie Y. [4 ]
Zhang, Qiming [1 ,2 ]
Liu, Zhouzerui [1 ,2 ]
Dong, Minghui [1 ,2 ]
Hu, Xueda [1 ,2 ]
Ouyang, Wenjun [4 ]
Peng, Jirun [5 ,6 ,7 ]
Zhang, Zemin [1 ,2 ,3 ]
机构
[1] Peking Univ, BIOPIC, Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China
[2] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China
[3] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
[4] Amgen Inc, Dept Inflammat & Oncol, San Francisco, CA 94080 USA
[5] Capital Med Univ, Beijing Shijitan Hosp, Dept Surg, Beijing 100038, Peoples R China
[6] Peking Univ, Sch Clin Med 9, Beijing 100038, Peoples R China
[7] Capital Med Univ, Sch Oncol, Beijing 100038, Peoples R China
基金
中国国家自然科学基金;
关键词
IMMUNE CHECKPOINT BLOCKADE; RNA-SEQ ANALYSIS; HEPATOCELLULAR-CARCINOMA; MAIT CELLS; LYMPHOCYTES; IMMUNOTHERAPY; EXHAUSTION; THERAPY; IMMUNOPATHOGENESIS; EXPRESSION;
D O I
10.1016/j.cell.2017.05.035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:1342 / +
页数:31
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