title: Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model.
abstract: Accumulating evidence suggests that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) are elevated in cancer patients and tumor-bearing hosts, and that depletion of Tregs and MDSC may enhance the anti-tumor immunity of the host. Sorafenib, a novel multi-kinase inhibitor, is approved for the treatment of several human cancers, including advanced hepatocellular carcinoma (HCC). Sorafenib is believed to inhibit tumor growth via anti-angiogenesis, cell cycle arrest, and inducing apoptosis. However, the impact of Sorafenib on immune cell populations in tumor-bearing hosts is unclear. In this report, we show that Tregs and MDSC are increased in the spleens and bone marrows of the BALB/c mice with liver hepatoma. The increase in Tregs and MDSC was positively correlated with tumor burden. Treatment of Sorafenib not only inhibited HCC cell growth in mice but also significantly decreased the suppressive immune cell populations: Tregs and MDSC. In conclusion, our study strongly suggests that Sorafenib can enhance anti-tumor immunity via modulating immunosuppressive cell populations in the murine liver cancer model.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mengde
authors.initials: M
authors.lastname: Cao
authors.forename: Yiling
authors.initials: Y
authors.lastname: Xu
authors.forename: Je-in
authors.initials: JI
authors.lastname: Youn
authors.forename: Roniel
authors.initials: R
authors.lastname: Cabrera
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Zhang
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gabrilovich
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018450:Disease Progression; D007111:Immunity, Cellular / Q000187:drug effects; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D013154:Spleen / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib