Cancer Cell：中山大学刘卓炜/马梓坤等揭示成纤维细胞脂质氧化重编程，增强T细胞抗肿瘤免疫及治疗响应

Core Viewpoint - The study identifies a chemotherapy-induced PTGER3+ cancer-associated fibroblast (CAF) subgroup characterized by enhanced lipid oxidation, termed lipo-CAF, which promotes CD8+ T-cell activation and cytotoxicity, thereby enhancing anti-tumor immunity and therapeutic response [2][3][9] Group 1: Mechanism and Findings - The research reveals a previously unrecognized metabolic adaptation mechanism in CAFs that supports CD8+ T-cell immunity, highlighting the role of lipid oxidation driven by CAFs in regulating CD8+ T-cell PTEN signaling as a potential pathway to enhance chemotherapy and immunotherapy efficacy [3][8] - Lipo-CAF specifically secretes lipid oxidation products like 11-HETE, which acts as an endogenous lipid ligand on CD8+ T-cells, inhibiting PTEN function and enhancing T-cell cytotoxicity and anti-tumor immune function [6][9] - The study emphasizes that the metabolic reprogramming of CAFs under chemotherapy conditions fine-tunes T-cell function, providing a theoretical basis for understanding the synergy between chemotherapy and anti-tumor immune responses [8][9] Group 2: Clinical Implications - A higher proportion of treatment-induced PTGER3+ CAFs is associated with improved therapeutic responses and better patient prognosis [2] - The findings suggest that 11-HETE supplementation could enhance the efficacy of chemotherapy and immunotherapy, indicating a potential new intervention strategy based on tumor microenvironment metabolic characteristics [9]