Cell子刊：老药新用！沈柏用/符达团队发现降脂药瑞舒伐他汀有望增强糖尿病相关胰腺癌的免疫治疗

Core Viewpoint - The study reveals a lactate-METTL16-CTCF signaling axis that links metabolic stress to immune evasion in diabetes-related pancreatic ductal adenocarcinoma (PDAC), suggesting potential strategies for enhancing immunotherapy in metabolically dysregulated pancreatic cancer [2][8]. Group 1: Research Findings - Tumor-associated Schwann cells (TASC) are remodeled under metabolic stress, serving as a key mediator of immune suppression in diabetes-related PDAC [4][7]. - A specific TASC subpopulation enriched in diabetes-related tumors was identified, characterized by METTL16, CD276, and NECTIN2, which impairs CD8+ T cell function and promotes PD-1 resistance [4][7]. - Lactate enters TASC via MCT1/MCT4, inducing lactylation of METTL16, enhancing CTCF stability, and activating immune suppressive ligands [5][7]. Group 2: Therapeutic Implications - Reducing METTL16 levels in Schwann cells can restore immune surveillance and increase tumor sensitivity to PD-1 blockade therapy [5][7]. - Rosuvastatin, a commonly used statin, was found to directly bind METTL16 and reduce its activity, leading to decreased immune suppressive molecules and increased CD8+ T cell proportions in diabetes-related PDAC patients [5][7]. - The combination of rosuvastatin with immunotherapy significantly enhances treatment efficacy in these patients [5][7].