Sorafenib inhibits interferon production by plasmacytoid dendritic cells in hepatocellular carcinoma

BackgroundSorafenib 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 type I interferon alpha (IFN alpha) in cancer microenvironments. However, the effects of sorafenib on the function of pDCs have not been evaluated in detail. MethodsNormal and patient PBMCs were stimulated with CpG-A to evaluate IFN alpha production with Flow cytometry and ELISA. ResultWe analyzed the production of IFN alpha by PBMCs in patients with advanced HCC under sorafenib treatment. We found that sorafenib-treated HCC patients produced less IFN alpha than untreated patients. Furthermore, we demonstrated that sorafenib suppressed the production of IFN alpha by PBMCs or pDCs from heathy donors in a concentration-dependent manner. ConclusionSorafenib 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.

Automated summary

The study found that sorafenib suppressed the function of plasmacytoid dendritic cells (pDCs) and inhibited the production of interferon alpha (IFN-α) by peripheral blood mononuclear cells (PBMCs) or pDCs from healthy donors in a concentration-dependent manner. This suggests that the immunosuppressive effect of sorafenib on pDCs should be considered during cancer treatment.