Immunotherapy in hepatocellular cancer

Hepatocellular carcinoma is a major global healthcare problem. It is closely related to chronic liver inflammation triggered by viral and non-viral insults, that can lead to exhaustion of effector T-cells. Furthermore, immune cells within the normal liver itself tend to be more immune tolerant in order to support the essential function of liver as the first processing station of molecules absorbed in the gastrointestinal tract. Dysregulation of the immune system is a hallmark of hepatocellular carcinoma. Immune checkpoint inhibitors targeting the programmed death-1 axis have shown promise as monotherapy in the management of advanced disease, but still most patients do not benefit from treatment. Most recently, combinatorial strategies with other immune checkpoint inhibitors or agents targeting the second hallmark of hepatocellular carcinoma, i.e., the activation of the vascular epithelial growth factor axis have been studied. In this paper, we review the current immunotherapy approaches for hepatocellular carcinoma and discuss novel immunotherapy approaches and optimal patient selection.