Hepatocarcinoma IVM · Spatiotemporal dynamics of CD8+ T cell responses to hepatocellular carcinoma

Spatiotemporal dynamics of CD8+ T cell responses to hepatocellular carcinoma

The hepatocellular carcinoma (HCC) is one of the most common primary liver tumour, is derived from hepatocytes and it is the second cause of cancer-related death all over the world. HCC has an aggressive nature and a poor prognosis; indeed it is the second most common cause of cancer-related mortality but only the sixth most common cause of cancer worldwide. Chronic liver disease and cirrhosis are the most important risk factors to develop HCC (85-90% incidence). Liver cirrhosis often is a resultant of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and autoimmune hepatitis. Since CD8+ T cells are thought to play a critical role in controlling HCC, and since the protective capacity is mediated by antigen-experienced effector cells and depends on their ability to migrate to the liver, recognize tumor antigens and deploy effector functions, in this project we studied the role of CD8+ T cells in a novel murine model of HCC. While some of the rules that characterize CD8+ T cell behavior in the cancerous liver have been characterized at the population level, we have limited knowledge of the dynamics of CD8+ T cell interactions with tumor and hepatic cells at the single-cell level. Although recent advances in intravital microscopy may enable us to investigate the extent to which anatomical and hemodynamical cues that characterize HCC differently shape CD8+ T cell behavior and function, we still lack a proper mouse where to address these issues. In conclusion we developed a functional platform to study the immune system behaviour inside spontaneous HCC. This platform will be used to study cell activation and the therapeutic effect of anti-tumoral compounds.

Data: CORDIS, © European Union