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.
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei, PR China.
Qun
Q
Jiang
Haiming
H
Wei
Zhigang
Z
Tian
D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011070:Poly I-C / Q000627:therapeutic use*
D000950:Antigens, Ly; D000954:Antigens, Surface; D039521:CD11c Antigen; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D011070:Poly I-C