Liver cancer is a life-threatening disease, and its incidence is increasing globally. The most common form of liver cancer is hepatocellular carcinoma (HCC). Approximately half of patients with HCC, especially those at advanced disease stages, receive systemic therapies, including the tyrosine kinase inhibitors sorafenib and lenvatinib. Over the past few years, immune checkpoint inhibitors (ICIs) have changed the landscape of HCC treatment. In particular, the combination therapy with atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) significantly improved survival benefits compared with sorafenib as a single agent, a finding that has stimulated further preclinical and clinical development of immunotherapeutic approaches for treating HCC. In addition to ICIs, oncolytic immunotherapy and adoptive T cell therapy have also emerged as immunotherapeutic strategies. A major challenge is that the tumor microenvironment of HCC is usually immunosuppressive, leading to immune escape and immunotherapy resistance. Hence, combination therapies that could sensitize HCC to immunotherapy have become a growing area of investigation. In this review, we summarize recent advances in HCC immuno-oncology and review immunotherapeutic strategies that are under development for treating HCC.
Keywords: CAR T cells; combination immunotherapy; hepatocellular carcinoma; immune checkpoint inhibitors; immunotherapy; resistance.