title: Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow cells.
abstract: Sorafenib has been used for the treatment of liver cancer. However, its clinical impact on human immunity system remains poorly known. Our previous study has shown that sorafenib modulates immunosuppressive cell populations in murine liver cancer models. Here, we continue to report that low doses of sorafenib promotes the survival of murine bone marrow cells (BMCs) in a dose-dependent manner by up-regulating the anti-apoptotic protein survivin. Sorafenib induces differentiation of BMCs into suppressive dendritic cells that inhibit autologous T-cell proliferation and stimulate CD4(+) T cells to express increased IL-1β, IL-2, IL-4, IL-10, IFN-γ and TNF-α, and reduced levels of IL-6 and CD25, which indicates that sorafenib-induced dendritic cells represent a distinct cellular subset with unique properties. Taken together, our findings suggest that in addition to its anticancer effects, sorafenib has an immunoregulatory property that is apparent at low doses.
authors.affiliation: Department of Radiology, China Medical University Shengjing Hospital, Shenyang, China Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China zhaoxiangxuan@163.com xiangxuanzhao@163.com.
authors.forename: Xiangxuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Mengde
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Radiology, China Medical University Shengjing Hospital, Shenyang, China.
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Ton
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Radiology, China Medical University Shengjing Hospital, Shenyang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D056747:Immunomodulation; D008113:Liver Neoplasms / Q000188:drug therapy*; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D000077157:Sorafenib; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Sorafenib; T cells; bone marrow cells; dendritic cells; immunoreaction