Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

被引：572

作者：

Sun, Yunfan ^{[1
,2
,4
]}

Wu, Liang ^{[3
,4
,5
]}

Zhong, Yu ^{[3
,6
]}

Zhou, Kaiqian ^{[1
,2
,4
]}

Hou, Yong ^{[3
,4
,5
,7
]}

Wang, Zifei ^{[3
,5
]}

Zhang, Zefan ^{[1
,2
,4
]}

Xie, Jiarui ^{[3
,6
]}

Wang, Chunqing ^{[3
,5
]}

Chen, Dandan ^{[3
]}

Huang, Yaling ^{[3
]}

Wei, Xiaochan ^{[3
]}

Shi, Yinghong ^{[1
,2
]}

Zhao, Zhikun ^{[3
]}

Li, Yuehua ^{[3
]}

Guo, Ziwei ^{[3
]}

Yu, Qichao ^{[3
]}

Xu, Liqin ^{[3
]}

Volpe, Giacomo ^{[8
]}

Qiu, Shuangjian ^{[1
,2
,4
]}

Zhou, Jian ^{[1
,2
,4
]}

Ward, Carl ^{[8
]}

Sun, Huichuan ^{[1
,2
,4
]}

Yin, Ye ^{[3
]}

Xu, Xun ^{[3
,9
]}

Wang, Xiangdong ^{[4
]}

Esteban, Miguel A. ^{[3
,8
,10
,11
]}

Yang, Huanming ^{[3
,5
,9
]}

Wang, Jian ^{[3
,12
]}

Dean, Michael ^{[13
]}

Zhang, Yaguang ^{[14
]}

Liu, Shiping ^{[3
,5
,7
]}

Yang, Xinrong ^{[1
,2
,4
]}

Fan, Jia ^{[1
,2
,4
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, Shanghai 200032, Peoples R China

[2] Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai 200032, Peoples R China

[3] BGI Shenzhen, Beishan Ind Zone, Shenzhen 518083, Peoples R China

[4] Fudan Univ BGI, Zhongshan Hosp, Zhong Hua Precis Med Ctr, Shanghai 200032, Peoples R China

[5] Univ Chinese Acad Sci, BGI Educ Ctr, Shenzhen 518083, Peoples R China

[6] South China Univ Technol, Sch Biol & Biol Engn, Guangzhou 510640, Peoples R China

[7] BGI Shenzhen, Shenzhen Key Lab Single Cell Omics, Shenzhen 518100, Peoples R China

[8] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Integrat Biol, Guangzhou 510530, Peoples R China

[9] Guangdong Prov Key Lab Genome Read & Write, Shenzhen 518120, Peoples R China

[10] Chinese Acad Sci, Inst Stem Cells & Regenerat, Beijing 100101, Peoples R China

[11] Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou 510005, Peoples R China

[12] James D Watson Inst Genome Sci, Hangzhou 310008, Peoples R China

[13] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA

[14] Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China

来源：

CELL | 2021年 / 184卷 / 02期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

SUPPRESSES TUMOR-GROWTH; CD8(+) T-CELLS; RNA-SEQ; DENDRITIC CELLS; EXPRESSION; DNA; RECONSTRUCTION; INFLAMMATION; MACROPHAGES; EFFECTOR;

D O I：

10.1016/j.cell.2020.11.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of similar to 17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8(+) T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8(+) T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8(+) T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

引用

页码：404 / +

页数：34

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