Epigenetic STING silencing is developmentally conserved in gliomas and can be rescued by methyltransferase inhibition

The stimulator of interferon genes (STING) is a critical signaling transducer of cytosolic DNA sensing, eliciting IRF3- and NFκB-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 tumor-associated immune cells or stroma.