Sunitinib indirectly enhanced anti-tumor cytotoxicity of cytokine-induced killer cells and CD3⁺CD56⁺ subset through the co-culturing dendritic cells.
Cytokine-induced killer (CIK) cells have reached clinical trials for leukemia and solid tumors. Their anti-tumor cytotoxicity had earlier been shown to be intensified after the co-culture with dendritic cells (DCs). We observed markedly enhanced anti-tumor cytotoxicity activity of CIK cells after the co-culture with sunitinib-pretreated DCs over that of untreated DCs. This cytotoxicity was reliant upon DC modulation by sunitinib because the direct exposure of CIK cells to sunitinib had no significant effect. Sunitinib promoted Th1-inducing and pro-inflammatory phenotypes (IL-12, IFN-γ and IL-6) in DCs at the expense of Th2 inducing phenotype (IL-13) and regulatory phenotype (PD-L1, IDO). Sunitinib-treated DCs subsequently induced the upregulation of Th1 phenotypic markers (IFN-γ and T-bet) and the downregulation of the Th2 signature (GATA-3) and the Th17 marker (RORC) on the CD3⁺CD56⁺ subset of CIK cells. It concluded that sunitinib-pretreated DCs drove the CD3⁺CD56⁺ subset toward Th1 phenotype with increased anti-tumor cytotoxicity.
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Adisak
A
Wongkajornsilp
Valla
V
Wamanuttajinda
Kanda
K
Kasetsinsombat
Sunisa
S
Duangsa-ard
Khanit
K
Sa-ngiamsuntorn
Suradej
S
Hongeng
Kittipong
K
Maneechotesuwan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D017252:CD3 Complex; D019002:CD56 Antigen; D007211:Indoles; C522918:NCAM1 protein, human; D011758:Pyrroles; D007371:Interferon-gamma; D000077210:Sunitinib