Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer.

Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and , , , , , , and mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DRCD33MDSCs, where miR-107 was able to target and suppress expression of and genes. Dampened expression supported expansion of MDSCs , while decreased led to activation of the PI3K pathway, resulting in increased expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11bGr1 MDSCs in mouse peripheral blood and altering expression of , , , and in the MDSCs. Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting and genes, thereby may provide novel cancer therapeutics target for gastric cancer.