清华大学最新Cell子刊论文：开发新型STING激动剂，激活强大的抗病毒及抗肿瘤免疫

Core Viewpoint - The research identifies GNE-6468 as a novel STING agonist that effectively activates STING-mediated innate immune responses and shows potential applications in antiviral and antitumor immunotherapy [2][6]. Group 1: Mechanism of Action - The study reveals the mechanism by which PI4P and the chemical agonist GNE-6468 activate STING, demonstrating that GNE-6468 binds to a specific pocket in the transmembrane domain of STING, causing outward displacement of the TM3 helix without altering the conformation of the ligand-binding domain [3][4]. - The structural analysis shows that both PI4P and GNE-6468 induce STING oligomerization and immune response, confirming the critical role of their interaction in STING activation [3][4]. Group 2: Functional Implications - GNE-6468 mediates a strong antiviral and antitumor immune response in a STING-dependent manner, indicating its potential as a therapeutic agent [4][6]. - The combination of GNE-6468 with PD-1 antibodies exhibits significant synergistic antitumor effects, highlighting its promising application in immunotherapy [3][4].