Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Abstract

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and has a high mortality rate. The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage. The recent description of the tumor microenvironment (TME) in HCC has provided a new concept of immunogenicity within the HCC. Virus-related HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells. This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors (ICIs). In addition, the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity. Therefore, data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Keywords: Hepatocellular carcinoma; Tumor immune microenvironment; Immune checkpoint inhibitor; Atezolizumab; Bevacizumab; Pembrolizumab

Core Tip: Hepatocellular carcinoma (HCC) is a prototype of inflammation-associated cancer. Its varied etiology from viral to alcohol and non-alcoholic steatohepatitis, tumor extent, intrahepatic spread, vascular invasion and metastases along with the underlying severity of liver dysfunction make it a complex scenario for adequate management. The recent elaboration of the tumor microenvironment revealing an immunogenic milieu and bringing the concept of “Cold” and “Hot” tumor opened the way for evaluation of immunotherapy in HCC. In recent years, with use of immune checkpoint inhibitors, there is a paradigm shift in the management of advanced and unresectable HCC. With the use of combination regimens including immune checkpoint inhibitors and transarterial chemoembolization/ablation/tyrosine kinase inhibitors, there is an ongoing effort to improve disease outcomes and minimize adverse events.