IRF3 and central nervous system cancer: Hypermethylation of the STING promoter that reduces STING expression has been reported in gliomas, melanoma, Hepatitis C, and small cell lung cancer.33,79–82 Based on such observations the combination of a STING agonist with a demethylating agent has been investigated in gliomas, melanoma, and gastric adenocarcinoma.33,79,81 As a proof-of-principle demonstration, STING agonist-resistant glioma cells treated with 5-aza-2'-deoxycytidine and STING agonist responded with increased expression of IRF3 and IFIT1 that are downstream markers of STING activation.