Background: 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.
Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1 , DICER1 , PTEN , PI3K , AKT , mTOR , and NF-kB  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.
Results: 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-DR^-CD33⁺MDSCs, where miR-107 was able to target and suppress expression of DICER1  and PTEN  genes. Dampened DICER1  expression supported expansion of MDSCs , while decreased PTEN  led to activation of the PI3K pathway, resulting in increased ARG1  expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b⁺Gr1^+/high MDSCs in mouse peripheral blood and altering expression of DICER1 , PTEN , ARG1 , and NOS2  in the MDSCs.
Conclusions: 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 DICER1  and PTEN  genes, thereby may provide novel cancer therapeutics target for gastric cancer.
Keywords: exosome, miRNA-107, myeloid-derived suppressor cell, arginase 1, gastric cancer