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Sorafenib inhibits interferon production by plasmacytoid dendritic cells in hepatocellular carcinoma
Xinning Zhang1,2,3,4, Yong Xu1,2,3, Guodong Zhao1,2,3
1Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.
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 type I interferon alpha (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 IFNα production with Flow cytometry and ELISA.
Result:
We analyzed the production of 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.
Insights
Sorafenib, a cancer drug, was found to suppress plasmacytoid dendritic cell (pDC) function and reduce interferon alpha (IFNα) production. This immunosuppressive effect of sorafenib on pDCs warrants consideration during cancer therapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Sorafenib is a multi-kinase inhibitor used for advanced hepatocellular carcinoma (HCC).
- Sorafenib influences immune cells, but its specific impact on plasmacytoid dendritic cells (pDCs) is unclear.
- pDCs are often impaired in cancer, producing insufficient type I interferon alpha (IFNα).
Purpose of the Study:
- To investigate the effects of sorafenib on pDC function, specifically IFNα production.
- To evaluate the clinical relevance of sorafenib's impact on pDCs in HCC patients.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from healthy donors and HCC patients were stimulated with CpG-A.
- Interferon alpha (IFNα) production was measured using flow cytometry and ELISA.
- Sorafenib's effect on IFNα production by PBMCs and pDCs was assessed in a dose-dependent manner.
Main Results:
- Sorafenib treatment in advanced HCC patients correlated with reduced IFNα production.
- Sorafenib significantly suppressed IFNα production by PBMCs and pDCs from healthy donors.
- The suppression of IFNα production by sorafenib was concentration-dependent.
Conclusions:
- Sorafenib suppresses the function of plasmacytoid dendritic cells (pDCs).
- The immunosuppressive effects of sorafenib on pDCs should be considered in clinical practice.
- Further research may explore strategies to mitigate sorafenib's impact on pDC-mediated immunity.
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