Mouse models of oncoimmunology in hepatocellular carcinoma.

Liver cancer is the fourth-leading cause of cancer-related mortality worldwide and incidence is on the rise. HCC is the most common form of liver cancer, with a complex etiology and limited treatment options. The standard of care treatment for advanced HCC patients is sorafenib, a tyrosine kinase inhibitor that offers limited survival benefit. In the past years, therapeutic options for the treatment of advanced HCC have increased substantially, including additional multikinase inhibitors as well as immune-checkpoint inhibitors. Nivolumab and pembrolizumab were approved in 2017 and 2018, respectively, as second-line treatment in advanced HCC. These drugs, both targeting the programmed death-1 (PD-1) pathway, demonstrate unprecedented results, with objective response rates of approximately 20%. However, the majority of patients do not respond, necessitating the identification of biomarkers of response and resistance to immunotherapy. With the recent success of immunotherapies in oncology, mouse models that better recapitulate the human disease and anti-tumor immune response are needed. This review lists ongoing clinical trials testing immunotherapy in HCC, briefly discusses the unique immunosuppressive environment of the liver, then delves into the most applicable current murine model systems to study oncoimmunology within the context of HCC, including syngeneic, genetically-engineered, and humanized models.