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Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic:polycytidylic acid treatment in mouse tumor models.


ABSTRACT: Polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, acts on myeloid cells and induces potent antitumor immune responses including natural killer (NK) cell activation. Myeloid-derived suppressor cells (MDSCs) systemically exist in tumor-bearing hosts and have strong immunosuppressive activity against antitumor effector cells, thereby dampening the efficacy of cancer immunotherapy. Here we tested what happened in MDSCs in poly I:C-treated mice. NK-sensitive syngenic tumor (B16)-bearing C57BL/6 mice were employed for this study. Intraperitoneal poly I:C treatment induced MDSC activation, driving CD69 expression and interferon (IFN)-? production in NK cells. IFN-? directly inhibited proliferation of B16 cells. This NK cell priming led to growth retardation of B16 tumors, although no direct tumoricidal activity was induced in NK cells. Mechanistic analysis using KO mice and function-blocking monclonal antibody revealed that MDSCs produced IFN-? via the mitochondrial antiviral signaling protein (MAVS) pathway after in vivo administration of poly I:C, and activated NK cells through the IFNAR pathway. MDSC-mediated NK cell priming was reconstituted by IFN-? in a coculture system. Either the MAVS or IFNAR signaling pathway was required for activation of MDSCs that led to growth retardation of B16 tumor in vivo. The results infer that MDSC is a target of poly I:C to prime NK cells, which exert antitumor activity to NK-sensitive tumor cells.

SUBMITTER: Shime H 

PROVIDER: S-EPMC6741616 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic:polycytidylic acid treatment in mouse tumor models.

Shime Hiroaki H   Kojima Ayako A   Maruyama Akira A   Saito Yusuke Y   Oshiumi Hiroyuki H   Matsumoto Misako M   Seya Tsukasa T  

Journal of innate immunity 20131029 3


Polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, acts on myeloid cells and induces potent antitumor immune responses including natural killer (NK) cell activation. Myeloid-derived suppressor cells (MDSCs) systemically exist in tumor-bearing hosts and have strong immunosuppressive activity against antitumor effector cells, thereby dampening the efficacy of cancer immunotherapy. Here we tested what happened in MDSCs in poly I:C-treated mice. NK-sensitive syngenic tumor  ...[more]

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