Evading the STING: LKB1 loss leads to STING silencing and immune escape in KRAS-mutant lung cancers

Abstract

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 the STING pathway may boost anticancer immune response in cancers with resistance to immune-checkpoint blockade.