Roles of the Immune System in the Development and Progression of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) typically arises within a background of underlying chronic liver disease. Persistent inflammation is the key element underpinning its development, regardless of the underlying aetiology of chronic liver disease. Several immunological mechanisms can impact the HCC development and progression, as well as response to treatments. Furthermore, there is increasing hope that targeting the immune response itself can be exploited as a therapeutic strategy. Many patients develop antigen-specific adaptive immune responses; however, the background of the liver as a tolerogenic organ and the tumour cells foster an immunosuppressive niche that prevents antigen-mediated clearance of tumour cells. Inhibitory immune mechanisms, such as the presence of regulatory T cells, macrophages and neutrophils with a pro-tumour phenotype, release of anti-inflammatory factors and expression of inhibitory receptors (e.g., cytotoxic T-lymphocyte-associated protein 4 or programmed cell death 1 receptor), contribute for the maintenance of that immunosuppressive microenvironment. This review summarises the knowledge on the contribution of the different immune system elements towards tumour development and progression, as well as current immunotherapeutic approaches being explored in the field.