Role of Immunity in Pathogenesis and Treatment of Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide with a high mortality. The available treatment options are limited, thus the development of new therapeutic approaches is of a high clinical significance. Key Messages: The immune system plays a central role in the pathogenesis of HCC by supporting tumor growth, tumor survival, angiogenesis and the development of vascular infiltration and metastasis. In contrast, the immune system also exhibits a protective role in tumor surveillance, and specific CD8⁺ T-cells can be detected for various tumor-associated antigens. However, antitumoral potential of the immune system is limited by various inhibitory mechanisms, for example, an impaired priming and activation of CD8⁺ T-cells, inhibitory cells (e.g., regulatory T-cells) or the expression of inhibitory receptors (e.g., programmed cell death-1 and cytotoxic T-lymphocyte antigen-4). Immunotherapeutic strategies addressing these inhibitory mechanisms, for example, by providing a source of tumor antigens, depleting immunosuppressive cells or blocking inhibitory receptors, aim to induce and boost naturally occurring antitumoral immune responses. Conclusion: HCC is a tumor with a high incidence and mortality in developing countries as well as in the Western world. Due to the immune system's central role in the pathogenesis and surveillance of HCC, immunotherapy is a new treatment option that has yielded first promising results.