Novel immunotherapeutic approaches for hepatocellular carcinoma treatment.

INTRODUCTION: The introduction of immune checkpoint inhibitors has been lately proposed for the treatment of hepatocellular carcinoma (HCC) with respect to other cancer types. Several immunotherapeutic approaches are now under evaluation for HCC treatment including: i) antibodies acting as immune checkpoint inhibitors; ii) antibodies targeting specific tumor-associated antigens; iii) chimeric antigen receptor redirected T (CAR-T) cells targeting specific tumor-associated antigens; iv) vaccination strategies with tumor-specific epitopes. Areas covered: The review provides a wide description of the clinical trials investigating the efficacy of the main immunotherapeutic approaches proposed for the treatment of patients affected by HCC. Expert opinion: The balancing between immunostimulative and immunosuppressive factors in the context of HCC tumor microenvironment results in heterogeneous response rates to immunotherapeutic approaches such as checkpoint inhibitors, among HCC patients. In this context, it becomes crucial the identification of predictive factors determining the treatment response. A multiple approach using different biomarkers could be useful to identify the subgroup of HCC patients responsive to the treatment with a checkpoint inhibitor (as an example, nivolumab) as single agent, and to identify those patients in which other treatment regimens, such as the combination with sorafenib, or with locoregional therapies, could be more effective.