南方医科大学最新Cell子刊：揭示尿苷调控CD8⁺ T细胞抗肿瘤免疫新机制

Core Viewpoint - The research highlights the role of uridine as an immune metabolite that regulates CD8⁺ T cell activity, revealing a molecular mechanism by which cancer cells suppress anti-tumor immunity by depleting uridine levels in the tumor microenvironment [8]. Group 1: Research Findings - The study published in Cell Metabolism identifies a new mechanism by which uridine mediates N-glycosylation of CD45 protein, promoting CD8⁺ T cell anti-tumor immunity [3]. - It details the process and regulatory mechanisms of uridine depletion in the tumor microenvironment, proposing new therapeutic targets and combination treatment strategies for immune therapy resistance [3]. - The research indicates that SNX17 expression negatively correlates with CD8⁺ T cell infiltration and sensitivity to immune checkpoint blockade (ICB) therapy [5]. Group 2: Mechanisms and Implications - SNX17 regulates the metabolic microenvironment, inhibiting CD8⁺ T cell function, and its knockout leads to significantly increased uridine levels in tumor cell supernatants and tissues, which can activate CD8⁺ T cells and inhibit tumor growth in mice [5]. - The activation mechanism of uridine on CD8⁺ T cells involves its metabolism to UDP-GlcNAc, which promotes N-glycosylation of the key membrane protein CD45, enhancing TCR signaling and effectively activating CD8⁺ T cells [5]. - The upstream mechanism shows that SNX17 stabilizes the transcription factor RUNX2, preventing its lysosomal degradation, which in turn upregulates the expression of uridine-degrading enzyme UPP1, leading to uridine depletion in the tumor microenvironment [6]. Group 3: Clinical Relevance - The findings suggest that SNX17 could serve as a predictive biomarker for resistance to cancer immunotherapy, while uridine may represent a promising candidate for immunotherapeutic drugs [8].