Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China. Electronic address: wuliang@genomics.cn.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510640, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518100, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen 518120, China.
Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Institute for Stem Cells and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen 518120, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; James D. Watson Institute of Genome Science, Hangzhou 310008, China.
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute Rockville, MD 20850, USA.
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518100, China. Electronic address: liushiping@genomics.cn.
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China. Electronic address: yang.xinrong@zs-hospital.sh.cn.
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China. Electronic address: fan.jia@zs-hospital.sh.cn.
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 ∼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.
