Directly Blocks Innate Immunity
This molecule directly occupies the cGAMP-binding site of STING, blocking interferon signaling at its origin—a mechanism opposite to existing STING activators and a novel intervention node for tumor immunotherapy.
Guo-Dong, Lu · Meng, Ying · Yang, Qingqing · Luo, Shudi · Xiaoming, Jiang · Zheng, Yanhua · Wu, Lihui · Li, Shan · Wang, Zheng · Li, Min · Wu, Qingang · Liwei, Xiao · Rongxuan, Zhu · Xuxiao, He · Hu, Yanyan · Zhao, Hong · Xianglai, Ye · Tong, Yingying · Fang, Jing · Xu, Daqian · Xu, Jun · Yuan, Ying · Lu, Zhimin
Immunity 2026
Lactate directly binds the cGAMP-binding domain of STING, inhibiting cGAMP binding, STING activation, and IRF3-dependent cytokine expression
EGFR activation promotes PKM2 phosphorylation of LDHA at S161, increasing lactate production, suppressing immune cell infiltration, and promoting tumor growth
In human glioblastoma, elevated LDHA S161 phosphorylation correlates with reduced STING activation, diminished cytotoxic immune cell infiltration, and poor survival