MSCs within the glioma microenvironment upregulate miR-21 expression in MSC-Exos through a miR-21/SP1/DNMT1 positive feedback loop. miR-21 potentiates CD73 expression on MDSCs by activating the PTEN/PI3K/AKT/HIF-1α signaling pathway, thereby enhancing their immunosuppressive effects. Moreover, miR-21 promotes M2 macrophage polarization, stimulates the differentiation and activation of MDSCs, and suppresses T cell activation. This evidence concerns the gene PTEN and central nervous system cancer.