Immunomodulation in hepatocellular cancer

Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the United States in relation to mortality. HCC relies on a complex immunosuppressive network to modify the host immune system and evade destruction. Intrinsic to the liver's function and anatomy, native hepatic and immune cells produce many inhibitory cytokines that promote tolerogenicity and limit immune response. Since the introduction of sorafenib in 2008, no treatment has been able to demonstrate improved survival in patients with advanced HCC post disease progression treated with sorafenib. More recent studies have shown that sorafenib has an immunomodulatory function in addition to inhibition of multiple tyrosine kinases. Clinical trials have aimed to further enhance this immunomodulatory function with other treatments, most promisingly immune checkpoint inhibitors. Additionally, ongoing studies are using combinatorial approaches with immunomodulatory treatment and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation. This article will review recent data describing the immunosuppressive network in HCC, recent results of immunotherapies, and combinatorial approaches to treat advanced HCC.