Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma

Trends Mol Med. 2019 Nov;25(11):1010-1023. doi: 10.1016/j.molmed.2019.06.007. Epub 2019 Jul 25.

Abstract

Hepatocellular carcinoma (HCC) is an inflammation-induced and chemotherapy-resistant cancer. Dysregulated signaling in the transforming growth factor beta (TGF-β) pathway plays a central role in inflammation, fibrogenesis, and immunomodulation in the HCC microenvironment. This review dissects the genetic landscape of the TGF-β superfamily genes in HCC and discusses the essential effects of this pathway on the tumor immune microenvironment. We highlight the TGF-β signature as a potential biomarker for identifying individualized immunotherapeutic approaches in HCC. An improved understanding of the detailed mechanisms of liver cancer immunogenicity and the specific role of TGF-β in mediating immunotherapy resistance in HCC will provide important insights into HCC immune escape and promote the development of biomarker-derived combination immunotherapies for HCC.

Keywords: TGF-β signaling; hepatocellular carcinoma; immune genomic profiling; immunotherapy; tumor microenvironment.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / therapy
  • Gene Expression Profiling
  • Genomics
  • Humans
  • Immunotherapy
  • Liver Neoplasms / genetics
  • Molecular Targeted Therapy
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Transforming Growth Factor beta