Role of the Immune System in Hepatocellular Carcinoma: Implications for Existing and Novel Therapies

Currently available treatment options for HCC are very limited. Much of the ongoing research thus aims to develop novel therapeutic approaches. Importantly, many different studies could demonstrate a pivotal role for the immune system in determining patient survival in HCC. Indeed, different immunotherapies are currently under evaluation for HCC and other cancers. A class of immunotherapies termed checkpoint inhibitors has already gained approval for the treatment of melanoma, demonstrating the potency of this new class of cancer therapy. Since these therapies target the immune system and not the tumor, they may be transferable to HCC. The immune system may thus have a major role in the future therapy of HCC. Several lines of evidence indicate that the immune system may also have a different, tumorigenic role. It is actively involved in the chronic hepatic inflammation culminating in HCC and may thus represent a common pathway of hepatocarcinogenesis. In this chapter, we will summarize our current understanding of the dual role of the immune system in the development and control of HCC. We will furthermore discuss implications of these findings for existing and novel therapies.