Immunotherapy for hepatocellular carcinoma: Current and future

Abstract

Hepatocellular carcinoma (HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However, there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy, either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.

Keywords: Adoptive cell therapy; Cancer vaccine; Checkpoint inhibitor; Hepatocellular carcinoma; Immunotherapy; Liver cancer; Oncolytic virus.

Figure 1

Current approaches of immunotherapy. Summary of immunotherapeutic agents studied in hepatocellular carcinoma. CAR-T: Chimeric antigen receptor expressing T cell; CIK: Cytokine-induced killer; CTLA-4: Cytotoxic T-lymphocyte associated antigen 4; DC: Dendritic cell; LAG-3: Lymphocyte activation gene 3; NK: Natural killer; PD-1: Programmed cell death protein 1; TGF-β: Transforming growth factor-β; Tim-3: T-cell immunoglobulin and mucin-domain containing-3. ¹Licensed by Food and Drug Administration.