Evading the STING: LKB1 Loss Leads to STING Silencing and Immune Escape in KRAS-Mutant Lung Cancers

Summary: Mutations in STK11 (LKB1) are a major cause of primary resistance to immunotherapy in non–small cell lung cancer. Kitajima and colleagues dissect the underlying mechanism of this immune-resistant phenotype, demonstrating that LKB1 loss leads directly to suppression of stimulator of interferon genes (STING) and insensitivity to cytoplasmic double-strand DNA detection. Therapies that reactivate LKB1 or theSTING pathway may boost anticancer immune response in cancers with resistance to immune-checkpoint blockade. See related article by Kitajima et al., p. 34 .