Hepatocellular carcinoma (HCC) almost always arises in the setting of chronic liver inflammation. IL-17-producing CD4+ T helper cells (Th17) possess potent inflammatory properties, and have been associated with HCC initiation and progression in mice and humans.
Several reports recently demonstrated the role of dietary salt (NaCl) in promoting Th17 differentiation and Th17-mediated
autoimmune and inflammatory diseases. However, very little is known about the role of salt intake in HCC or other inflammation associated cancers. Based on published evidence, we hypothesize that excessive salt intake facilitates HCC development through Th17/IL-17-dependent mechanisms.
We will use two different models of HCC in mice. We will perform a non-drug clinical trial to test the effect of salt restriction in patients with compensated cirrhosis (which are at risk of developing HCC), and we will correlate urinary Na+ levels with the immune profile and risk of HCC in these patients. Our proposal may provide evidence supporting a new preventive measure (salt restriction) in this set of patients, as well as new evidence supporting the importance of IL- 17/Th17 axis as a therapeutic target in HCC.
