上海交通大学×广州医科大学合作最新Cell论文：发现铁死亡细胞的“免疫刹车”，释放GPX4来破坏抗肿瘤免疫

Core Viewpoint - The study reveals a novel regulatory axis involving GPX4 and ZP3 receptors that impairs antitumor immunity during ferroptosis, suggesting new therapeutic targets for cancer immunotherapy, especially for patients unresponsive to existing treatments [2][3][16]. Group 1: Mechanism of Action - The research identifies that during ferroptosis, cancer cells release GPX4 protein, which binds to ZP3 receptors on dendritic cells, activating a signaling cascade that inhibits glycolysis and impairs dendritic cell maturation and activation, leading to T cell activation defects [3][6][14]. - Disruption of the GPX4-ZP3 interaction can restore dendritic cell metabolic activity and enhance antitumor immunity, indicating a potential therapeutic strategy [3][16]. Group 2: Clinical Implications - Clinical data show that higher serum levels of GPX4 correlate with poorer treatment outcomes, and elevated ZP3 expression is associated with unfavorable prognosis across various solid tumors [16][18]. - In preclinical models, blocking the GPX4-ZP3 interaction significantly enhances the efficacy of chemotherapy, immunotherapy, and radiotherapy, providing a new approach to overcoming tumor resistance [16][19]. Group 3: Future Directions - The findings open avenues for personalized cancer immunotherapy by targeting the GPX4-ZP3 pathway, potentially benefiting patients who do not respond to current immunotherapies [18][19]. - Ongoing research aims to translate these discoveries into clinical applications, with the possibility of using GPX4 and ZP3 levels as biomarkers for tailored treatment strategies [19][20].