Glycolysis drives STING signaling to facilitate dendritic cell antitumor function

作者：Zhilin Hu, Xiaoyan Yu, Rui Ding, Ben Liu, Chuanjia Gu, Xiuwu Pan, Qiaoqiao Han, Yuerong Zhang, Jie Wan, Xingang Cui, Jiayuan Sun, Qiang Zou · 发表于：Journal of Clinical Investigation · 年份：2023 · DOI：10.1172/jci166031 · 被引用次数：99 · 研究领域：interferon and immune responses、Immune Response and Inflammation、Viral Infections and Vectors

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 DC activity in tissue samples from patients with non-small cell lung cancer. Our results provide mechanistic insight into how the crosstalk of glycolytic metabolism and STING signaling enhances DC antitumor activity and can be harnessed to improve cancer therapies.