Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma.
IF: 66.850
Cited by: 278


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.


Gene Expression
early-relapse tumor
hepatocellular carcinoma
immune microenvironment
immune therapy
single-cell RNA sequencing
tumor ecosystem

MeSH terms

CD8-Positive T-Lymphocytes
Carcinoma, Hepatocellular
Gene Expression Regulation, Neoplastic
Killer Cells, Natural
Liver Neoplasms
Myeloid Cells
Neoplasm Recurrence, Local
Single-Cell Analysis
Tumor Microenvironment


Sun, Yunfan
Wu, Liang
Zhong, Yu
Zhou, Kaiqian
Hou, Yong
Wang, Zifei
Zhang, Zefan
Xie, Jiarui
Wang, Chunqing
Chen, Dandan
Huang, Yaling
Wei, Xiaochan
Shi, Yinghong
Zhao, Zhikun
Li, Yuehua
Guo, Ziwei
Yu, Qichao
Xu, Liqin
Volpe, Giacomo
Qiu, Shuangjian
Zhou, Jian
Ward, Carl
Sun, Huichuan
Yin, Ye
Xu, Xun
Wang, Xiangdong
Esteban, Miguel A
Yang, Huanming
Wang, Jian
Dean, Michael
Zhang, Yaguang
Liu, Shiping
Yang, Xinrong
Fan, Jia

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