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 poly 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-gamma 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.