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

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Affiliations

  • 1. 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.
      Authors
    • Sun Y 1
    • Zhou K 1
    • Zhang Z 1
    • Qiu S 1
    • Zhou J 1
    • Sun H 1
    • Yang X 1
    • Fan J 1
    (8 authors)
  • 2. 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.
      Authors
    • Wu L 2
    (1 author)
  • 3. BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510640, China.
      Authors
    • Zhong Y 3
    • Xie J 3
    (2 authors)
  • 4. 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.
      Authors
    • Hou Y 4
    (1 author)
  • 5. BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
      Authors
    • Wang Z 5
    • Wang C 5
    (2 authors)
    • Show all (16)

ORCIDs linked to this article

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Cell, 23 Dec 2020, 184(2):404-421.e16
https://doi.org/10.1016/j.cell.2020.11.041 PMID: 33357445 

A comment on this article appears in "Dissecting Early Relapse in Liver Cancer, One Cell at a Time." Hepatology. 2021 Nov;74(5):2891-2893.

Abstract 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.cell.2020.11.041

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S0092867420316135/pdfUnpaywall

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Funding 

Funders who supported this work.

Chinese Academy of Sciences

    National Natural Science Foundation of China

      Natural Science Foundation of Guangdong Province

        Science and Technology Planning Project of Guangdong Province

          Science, Technology and Innovation Commission of Shenzhen Municipality

            Shanghai Association for Science and Technology

              Shanghai Municipal Health and Family Planning Commission