IFN-producing killer dendritic cells contribute to the inhibitory effect of poly I:C on the progression of murine melanoma

Toll-like receptor 3 agonist polyinosinic-polycytidilic acid (poly I:C) has been widely used as a potent adjuvant in tumor immunotherapy. In the present study, it was demonstrated that intraperitoneal injection of pole I:C could inhibit lung and liver metastasis of B16 melanoma cells in C57BL/6 mice in natural killer (NK) cells and interferon (IFN)-gamma dependent manner, leading to prolonged survival of the mice. B220(+) CD11c(+) NK1.1(+) cells, recently defined as IFN-producing killer dendritic cells (IKDCs) were markedly increased in the spleen, lung, and liver of poly I:C-treated tumor bearing mice, compared with the control group. IFN-gamma induction by poly I:C in this unique NK cell subset indicated its critical contribution in tumor suppression in this model. Meanwhile, results of in vitro culture assay showed that poly I:C synergized with B16 cells could significantly promote IKDCs expansion in lymphocytes from different organs along with IFN production. Moreover, these ex vivo expanded IKDCs also exerted cytolytic activities against B16 cells and YAC-1 cells as conventional NK cells did. In conclusion, the findings of this study provide new insights into the role of IFN-gamma and IKDCs in the antitumor effect of poly I:C, and will possibly be helpful to explain why poly I:C may work as an adjucant to improve the antitumor effects of innate cells.