Immunotherapy in hepatocellular carcinoma

Ann Hepatol. 2019 Mar-Apr;18(2):291-297. doi: 10.1016/j.aohep.2019.04.003. Epub 2019 Apr 25.


Hepatocellular carcinoma (HCC) is considered an immunogenic tumor that arises in chronically inflamed livers due to underlying chronic liver disease caused by viral and non-viral pathogenesis. This inflammation leads to tumor development and is associated to higher tumor immunogenicity. For this reason immunotherapeutic approaches may be suitable therapeutic strategies for HCC. Indeed, several preclinical and clinical data support this hypothesis showing that immunotherapy and even more their combination may be a good alternative candidate for the treatment of HCC patients. However, considering that the liver plays a central role in host defense as well as in the maintenance of self-tolerance, it is characterized by a strong intrinsic immune suppressive microenvironment as well as by a high immune evasion, which may represent a major impediment for an effective immune response against tumor. Furthermore, the low expression of tumor antigens on liver cancer cells leads to a lower T-cell activation and tumor infiltration, resulting in a less efficient control of the tumor growth and, consequently, in a worse clinical outcome. For this reason, strategies should be developed to counteract the different factors in the HCC tumor microenvironment playing a major role in reducing the effects of immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mutation
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tumor Escape / drug effects
  • Tumor Microenvironment


  • Antigens, Neoplasm
  • Antineoplastic Agents, Immunological
  • Cancer Vaccines