The impact of the CXC chemokine CXCL13 mediated B lymphocyte recruitment on the development and progression of hepatocellular carcinoma

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The hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide associated with a very poor prognosis with an overall survival rate of 3-5%. Most of the HCC develop on the background of pre-existing chronic liver diseases, e.g. chronic hepatitis B or C virus infections and non-alcoholic steatohepatitis, which are histopathologically characterized by a chronic intrahepatic inflammation. During this inflammation, the recruitment of inflammatory cells to the liver is mainly orchestrated by small, soluble molecules which are termed chemokines. Together with their specific receptors they form a very complex system within the liver mediating not only the infiltration and homing of intrahepatic leucocytes but also exhibiting direct modulatory effects on liver resident cells. Recently, it could be demonstrated that the expression of the CXC chemokine CXCL13 is significantly upregulated in the tissue of hepatocellular carcinoma compared to normal or preneoplastic liver samples. CXCL13, which binds to its specific receptor CXCR5, is known to be a selective and highly efficacious chemoattractant for B lymphocytes, a cell population which is enhanced in HCC lesions, and has been shown to exert direct stimulatory effects on various carcinoma cells. However, little is known about its role during chronic liver disease and especially during hepatic carcinogenesis. Therefore, the aim of this project is to identify and characterize the impact of an enhanced CXCL13 expression and the consecutive recruitment of B lymphocytes to the liver on the development and progression of hepatocellular carcinoma. These results should provide a new insight in the molecular mechanisms of hepatic carcinogenesis which could help to facilitate early diagnosis and identify new therapeutic targets in order to improve the prognosis of patients with HCC.