Immunotherapy in GI Cancers: Hepatocellular Carcinoma: Perspective

Abstract

AbstractCancer immunotherapy has finally entered the realm of hepatocellular carcinoma (HCC). The first immune checkpoint inhibitor (ICI) containing systemic treatment to be ever approved for HCC in the first-line setting is the combination of atezolizumab and bevacizumab which has produced previously unseen clinical outcomes in the advanced stage in the IMbrave150 trial. The relevance of these results for the field of HCC research can hardly be overstated. We contemplate in this perspective three key questions which arise from this success: (1) Which groups of HCC patients do or do not benefit from checkpoint inhibition? (2) Is immunotherapy effective at earlier HCC stages? 3. What immunotherapies beyond PD1/PD-L1/CTLA4 inhibition are effective? We summarize the current evidence regarding biomarkers for response prediction, give an overview of the currently ongoing clinical trials testing immunotherapeutic agents in earlier HCC stages, and highlight novel immune interventions for HCC which go beyond the established ICIs. In light of our understanding of the pathogenesis of HCC and emerging data from immunotherapeutic trials, it appears likely that the combination of atezolizumab and bevacizumab represents just the beginning of a much larger development that will fundamentally change the treatment and improve the outcome of patients with HCC.KeywordsClinical trialsHepatocellular carcinomaImmunotherapyLiver cirrhosissystemic treatmentTumour microenvironment