胰腺导管腺癌中脂质相关巨噬细胞的代谢调控与免疫抑制功能

We conducted a narrative review by systematically searching PubMed, Web of Science, and Scopus for articles on LAMs in PDAC up to December 2023. Key themes were synthesized to cover defining markers, metabolic pathways, immunosuppressive functions, and therapeutic strategies.

LAMs are characterized by co-expression of TREM2, APOE, CD9, and lipid-handling genes, and their accumulation correlates with poor prognosis. They undergo metabolic rewiring involving CD36-mediated lipid uptake, dysregulated cholesterol efflux, fatty acid oxidation, and de novo lipogenesis, which collectively enforce an immunosuppressive phenotype. LAMs interact bidirectionally with cancer-associated fibroblasts and directly suppress CD8+ T cells and NK cells. Preclinical targeting of CD36, TREM2, or FAO shows promise but faces challenges in toxicity and delivery. DISCUSSION: LAMs represent a potential therapeutic vulnerability in PDAC, but the field is still in its early stages. Future work should focus on establishing causal evidence in PDAC-specific models, developing tumor-selective delivery systems, and validating biomarkers for patient stratification.