Fig. 6

The immunomodulatory effect of exosomal miRNA in tumor microenvironments: Exosomes released by primary tumor cells are absorbed by receptors of the immune cells, wherein the exosomal miR-212-3p derived pancreatic cancer targets MHC II TF RFXAP result in reducing the expression of HLA-DR, -DP, and -DQ molecules which interfere with DCs cells function, miR-203 downregulates TLR4 and downstream cytokines in DCs, and miR-301a-3p induced the M2 polarization of macrophages via targeting PTEN and activation of the p-mTOR, p-AKT, PI3Kγ signaling pathway. In breast cancer, miR-let-7i induces DC maturation by decreasing TGF-β, SOCS1, and KLRK1 levels and increasing IL-6, IL-7, IFNγ, and IL-1b. miR-22-3p derived EOC activates macrophages to a TAM through SOCS3/STAT3 pathway. Also, miR-21-3p, miR-125B-5P, miR-181D-5p, and miR-940 induce M2 macrophage polarization.M2 polarization induced by miR-21 derived human head and neck cancer secrets miR-21 and miR-1246 derived colon cancer. DCs took up miR-142-3p, miR-150-5p derived Treg resulting in induction of a tolerogenic phenotype in these cells, with increased IL-10 and decreased IL-6 production, while miR-let-7d derived Treg inhibit Th1 proliferation and IFNγ. Glioblastoma secretes miR-10a and miR-21, which affect the activation and differentiation of MDSCs by targeting RORA and PTEN, respectively. These exosomal miRNAs modulate the immune microenvironment by mediating immunosuppression. While exosomal miR-125-5p-derived melanoma enhances immunity by increasing the level of M1 phenotype markers IL-1β, CCL1, CCL2, and CD80 via targeting LIPA. *( +): increase, (−): decrease