Sorafenib Inhibits Interferon Production by Plasmacytoid Dendritic Cells in Hepatocellular Carcinoma

Abstract Background：Sorafenib is a multi-kinase inhibitor that shows antitumor activity in advanced hepatocellular carcinoma. Sorafenib exerts a regulatory effect on immune cells, including T cells, natural killer cells and dendritic cells. Studies have shown that plasmacytoid dendritic cells (pDCs) are functionally impaired in cancer tissues or produce low IFNα in cancer microenvironments. However, the effects of sorafenib on the function of pDCs have not been evaluated in detail.Methods: Normal and patient PBMCs were stimulated with CpG-A to evaluate IFNa production with Flow cytometry and ELISA. Result: We analyzed the production of type I interferon (IFNα) by PBMCs in patients with advanced HCC under sorafenib treatment. We found that sorafenib-treated HCC patients produced less IFNα than untreated patients. Furthermore, we demonstrated that sorafenib suppressed the production of IFNα by PBMCs or pDCs from heathy donors in a concentration-dependent manner. Conclusion: Sorafenib suppressed pDCs function. Given that sorafenib is a currently recommended targeted therapeutic agent against cancer, our results suggest that its immunosuppressive effect on pDCs should be considered during treatment.