PGE2 is emerging as a key mediator of these effects, and both PGE2 and its upstream biosynthetic enzyme COX-2 are overexpressed in the GBM-TME, are associated with poor prognosis, and mediate pleiotropic effects that support glioma proliferation, angiogenesis, and immunosuppression (16, 34). This evidence concerns the gene PTGS2 and glioma.