Issues

Kitajima and colleagues found that KRAS-mutant/LKB1-null (KL) lung cancers exhibit upregulation of genes associated with oxidative stress and downregulation of genes involved in interferon signaling, including TMEM173, which encodes the dsDNA sensor STING A screen of epigenetic inhibitors revealed that inhibiting DNMT1 and EZH2 restored STING expression in STING-low KL cell lines, and the binding of DNMT1 to the TMEM173 promoter was increased in STING-null KL cell lines compared to STING-low KL cell lines Ectopic expression of LKB1 combined with inhibition of DNMT1 restored STING expression and pathway activation, and a STING agonist restored PD-L1 expression in KL cell lines Collectively, these findings demonstrate that LKB1 negatively regulates STING in KRAS-driven lung cancer and suggest potential therapeutic strategies for patients with KRAS-mutant/LKB1-null lung cancer For details, please see the article by Kitajima and colleagues on page 34.