STING agonists activate multiple regulated cell death mechanisms in monocytes

Abstract

Stimulation of the innate immune responses using agonist of pattern recognition receptors is one of the investigated therapeutic approaches for treatment of chronic diseases, such as cancer or chronic infections. The cyclic-GMP-AMP synthase -stimulator of interferon genes (cGAS-STING) pathway is one potential targetable pathway, as it naturally recognizes double-stranded DNA in the cytoplasm, and in turn triggers secretion of interferons and other proinflammatory cytokines1. The secreted cytokines further mediate various innate immune processes, some of which also induce adaptive immune responses against viral infection or tumors1,2.Importantly, the cGAS-STING pathway can be activated also by small molecules, STING agonists2.