Targeting Neoantigens In Hepatocellular Carcinoma For Immunotherapy: A Futile Strategy?

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide, accounting for 90% of liver cancers. Effective systemic treatments for advanced stage HCC are limited. The recent clinical application of mutated neoantigens as immunotherapeutic targets in several human cancers demonstrated that boosting host T cell responses to these antigens may help control patient tumors. With increased enthusiasm for targeting mutated neoantigens as a strategy in cancer immunotherapy, many clinical trials were initiated to apply mutated neoantigens as targets for the therapy of HCC and other solid tumors. However, recent studies suggest that targeting mutated neoantigens for the immunotherapy of HCC and other solid tumors has pitfalls and may not achieve efficacy without strategic changes. Herein, we discuss the limits of using neoantigens as targets in HCC immunotherapy and suggest alternative strategies to overcome these limits. Importantly, similar limits and alternative strategies are likely applicable to other intermediate and low tumor mutation burden cancers.