Targets of immunotherapy for hepatocellular carcinoma: An update

Abstract

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.

Keywords: Hepatocellular carcinoma, Immunotherapy, Immune checkpoint inhibitors, Adoptive cell therapy, Oncolytic vaccines, Combination therapy

Core Tip: A significant proportion of patients with hepatocellular carcinoma (HCC) present with advanced disease and therapeutic strategies for such patients are limited. The tumor microenvironment mediating immune response suppression, immune tolerance, and evasion further complicate the treatment in advanced HCC. The involvement of immune response in the pathogenesis of HCC makes immunotherapy an attractive approach for the treatment of advanced HCC. Further, the recent research with beneficial results with immune checkpoint inhibition, adoptive cell transfer therapy, tumor vaccines, and combinational therapies to boost the immune response of the tumor are in development and have been discussed here.