Successful tumor immunotherapy requires not only potent anti-tumor cytotoxicity, but also overcoming the local immunosuppression. The immunosuppression in the tumor microenvironment has been attributed to either the tumor itself or the tumor-associated macrophages (TAM). 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 coculture 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 proinflammatory 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.