NKG2D ligand RAE1? induces generation and enhances the inhibitor function of myeloid-derived suppressor cells in mice.

ABSTRACT: Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8⁺ T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D-mediated immune cell activation, such as tumour-derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down-regulate the expression of NKG2D on NK cells and CD8⁺ T cells. Here, we report that surface NKG2D ligand RAE1? on tumour cells induces CD11b⁺ Gr-1⁺ myeloid-derived suppressor cell (MDSC) via NKG2D in vitro and in vivo. MDSCs induced by RAE1? display a robust induction of IL-10 and arginase, and these MDSCs show greater suppressive activity by inhibiting antigen-non-specific CD8⁺ T-cell proliferation. Consistently, upon adoptive transfer, MDSCs induced by RAE1? significantly promote CT26 tumour growth in IL-10- and arginase-dependent manners. RAE1? moves cytokine balance towards Th2 but not Th1 in vivo. Furthermore, RAE1? enhances inhibitory function of CT26-derived MDSCs and promotes IL-4 rather than IFN-? production from CT26-derived MDSCs through NKG2D in vitro. Our study has demonstrated a novel mechanism for NKG2D ligand⁺ tumour cells escaping from immunosurveillance by facilitating the proliferation and the inhibitory function of MDSCs.

SUBMITTER: Qian L 

PROVIDER: S-EPMC5571551 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature