The stimulator of interferon genes (STING) is a critical signaling transducer of cytosolic DNA sensing, eliciting IRF3-and NFkB-dependent transcription of type I IFNs and pro-inflammatory cytokines. The importance of tumor-localized STING activation in priming endogenous antitumor immunity is well established. A pan-cancer analysis showed that STING signaling is frequently disrupted through loss-of-function mutations or hypermethylation of the STING or cGAS promoters (Konno et al., 2018). Here we investigate STING signaling in glioblastoma (GBM) and normal brain and find that STING expression is suppressed in both normal brain and glioma cells, but not in tumorassociated immune cells or stroma. We identify a CpG site that is methylated in normal brain, gliomas, and other neuroectoderm-derived cancers, but not in most extracranial cancers. We demonstrate that STING expression is rescued by decitabine, a DNA methyltransferase inhibitor (DNMTi) that is used to treat myelodysplastic syndrome and acute myeloid leukemia. Our work raises the potential of DNMTis to reconstitute STING signaling in GBM tumor cells.