Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Nat Commun. 2021 Jun 17;12(1):3684. doi: 10.1038/s41467-021-24010-1.

Abstract

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Proliferation
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Hepatitis B virus / genetics
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nectins / genetics
  • Nectins / metabolism
  • Principal Component Analysis
  • Prognosis
  • RNA-Seq
  • Receptors, Immunologic / metabolism
  • Single-Cell Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • NECTIN2 protein, human
  • Nectins
  • Receptors, Immunologic
  • TIGIT protein, human