Targeting STING to promote antitumor immunity

Pharmacology-based methods that promote antitumor immunity have the potential to be highly efficacious while avoiding the systemic cytotoxicity associ-ated with traditional chemotherapies. Activation of type I interferon (IFN) signal-ing in antigen-presenting cell types [e.g., macrophages and dendritic cells (DCs)] is critical, if not essential, for inducing a tumor-specific adaptive immune response, including the activation of cytolytic CD8 T cells. In the context of pro-moting antitumor immunity, the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway has emerged as a principal regulator of essential type I IFN signaling. As such, STING represents a highly attractive target for de-veloping a first-in-class immunotherapy, albeit one with a potential for significant cell type-and downstream pathway-dependent on-target toxicities, as well as conceivable pharmacogenomic liabilities.