Immunomodulation for hepatocellular carcinoma therapy: current challenges.

Abstract

The emergence of novel immunotherapies, such as immune-checkpoint inhibitors has changed the landscape of systemic cancer treatment. In hepatocellular carcinoma (HCC) patients, despite initial enthusiasm, the proportion of responders to immune-checkpoint inhibitors remains low. We provide a brief update of this rapidly evolving field, with specific focus on the development in the field of predictive factors and the immunomodulation induced by locoregional therapies. Even if the immune contexture of HCC before the treatment remains the most promising predictive marker for response to immunotherapies, recent findings show that the cause of HCC may have also a key role. Specific inflammatory mechanisms induced by NASH may result in limited efficacy of immunotherapy compared with viral HCC. Other recent findings showed that percutaneous ablations are responsible for intratumoral immune changes and systemic immune system activation that may help to prevent recurrence when combined with immunotherapies. In case of multifocal HCC, transarterial therapies (TACE and SIRT) may help to turn a cold tumor type to a hot tumor type and could be associated with immune-checkpoint inhibitors to improve outcomes. The future HCC management will focus on patient stratification for specific immunotherapies depending on the signature and cause of HCC and the best combined approaches in which locoregional therapies may play a pivotal role.