Interferon-gamma is a key cytokine in tumor immunosurveillance. The recently described interferon-producing killer dendritic cell (IKDC), can be distinguished from other innate effectors by its ability to kill a large variety of tumor cells and to produce high amounts of interferon-gamma after encountering tumors in the absence of exogenous cytokines. The cytotoxic activity of IKDC was unraveled during an efficient immunotherapy combining c-kit tyrosine kinase inhibitors and interleukin-2, and is mediated through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon type IIR.