In a recent study published in Cancer Cell, Low et al. shed a light on a novel DNA methylation pattern in the promoter region of the stimulator of interferon genes (STING), which may be a key factor for the “cold” tumor micro-environment (TME) of glioblastoma (GBM), contributing to its immunosuppression. 1 They have demonstrated that STING expression is epigenetically silenced by cg16983159 methylation in glioma cells as well as normal brain cells and this silencing can be rescued by DNA methyltransferase (DNMT) inhibition (Fig. 1). 1

Cancer cells, especially those treated with radiation or chemotherapy, often contain high levels of cytosolic DNA. 2 The cGAS–STING signaling axis is the major sensor of cytosolic DNA and triggers the innate immune response. 3 Cyclic GMPAMP (cGAMP) produced by cGAMP synthase (cGAS) binds to STING and activates STING signaling, leading to the production of a series of pro-inflammatory cytokines, such as type I interferons (IFNs)(Fig. 1). 3 Pro-inflammatory cytokine production and T-cell infiltration are important features of the socalled “hot” TME (T-cell inflamed), whereas the “cold” tumors (non-T-cell inflamed) are characterized by T-cell absence. The “hot” tumors are generally more responsive to immunotherapy,