Sorafenib Inhibits Interferon Production by Plasmacytoid Dendritic Cells in Hepatocellular Carcinoma

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2022 Nov 30

PMID 36451110

Authors

Xinning Zhang

Yong Xu

Guodong Zhao

Rong Liu

Haisheng Yu

Affiliations

Soon will be listed here.

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 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.

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