(The) role of activated hepatic stellate cells and myeloid-derived suppressor cells during the hepatic tumorigenesis

Abstract

In the liver, 80% of hepatocellular carcinoma (HCC) development in a microenvironment is characterized by chronic injury, inflammation, as well as fibrosis. However, certain cellular mediators which are responsible for the high risk to promote HCC are not well studied, unfortunately. Here we investigated the hypothesis that hepatic stellate cells (HSCs) promote HCC, a consequence of recruiting of myeloid-derived suppressor cells (MDSCs) which known as immunosuppressive cells. In the study of HCC mouse models and analyses of HCC patient specimens, activated HSCs near hepatic tumor site dramatically induced infiltration of MDSCs. After MDSCs interacting with HSCs accelerated tumor progression by inhibiting proliferation of cytotoxic T lymphocyte via arginase-I dependent manner. Our data suggest that the activation of MDSCs by HSCs might contribute to immune suppression during hepatic tumor progression. Therefore, the interaction of activated HSCs and MDSCs might be the new therapeutic targets for prevention of HCC