Glycolysis drives STING signaling to facilitate dendritic cell antitumor function.

ABSTRACT: Activation of STING signaling in DCs promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark of activated DCs, but how the glycolytic pathway intersects with STING signaling in tumor-infiltrating DCs remains elusive. Here, we show that glycolysis drives STING signaling to facilitate DC-mediated antitumor immune responses. Tumor-infiltrating DCs exhibited elevated glycolysis, and blockade of glycolysis by DC-specific Ldha/Ldhb double deletion resulted in defective antitumor immunity. Mechanistically, glycolysis augmented ATP production to boost STING activation and STING-dependent DC antitumor functions. Moreover, DC-intrinsic STING activation accelerated HIF-1α-mediated glycolysis and established a positive feedback loop. Importantly, glycolysis facilitated STING-dependent

SUBMITTER: Hu Z 

PROVIDER: S-EPMC10065062 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature