Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities

Mol Cancer. 2019 Aug 29;18(1):130. doi: 10.1186/s12943-019-1047-6.

Abstract

Incidence of hepatocellular carcinoma (HCC) is on the rise due to the prevalence of chronic hepatitis and cirrhosis. Although there are surgical and chemotherapy treatment avenues the mortality rate of HCC remains high. Immunotherapy is currently the new frontier of cancer treatment and the immunobiology of HCC is emerging as an area for further exploration. The tumor microenvironment coexists and interacts with various immune cells to sustain the growth of HCC. Thus, immunosuppressive cells play an important role in the anti-tumor immune response. This review will discuss the current concepts of immunosuppressive cells, including tumor-associated macrophages, marrow-derived suppressor cells, tumor-associated neutrophils, cancer-associated fibroblasts, and regulatory T cell interactions to actively promote tumorigenesis. It further elaborates on current treatment modalities and future areas of exploration.

Keywords: Hepatocellular carcinoma; Immunotherapy; Macrophages; Myeloid suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / therapy
  • Humans
  • Immunomodulation*
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Myeloid-Derived Suppressor Cells / immunology
  • Myeloid-Derived Suppressor Cells / metabolism
  • Myeloid-Derived Suppressor Cells / pathology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Tumor Microenvironment / immunology*