Macrophage Lipid Metabolism: A Metabolic Hub in the Tumor Microenvironment and Novel Therapeutic Target, from Mechanistic Insights to Clinical Translation

Lipid metabolism reprogramming in the tumor microenvironment critically drives cancer progression. Tumor-associated macrophages (TAMs), acting as central hubs, promote immunosuppression and metastasis through lipid uptake, processing, and signaling, thereby shaping TAMs' pro-tumor functions. This review systematically examines TAM lipid metabolism mechanisms, focusing on lipid absorption, intracellular handling, and pro-tumorigenic metabolic signaling. It highlights the local-systemic lipid network, revealing TAMs sustain tumor metabolic demands by coordinating bidirectional lipid flux and integrating the SREBP pathway for dynamic balance. Targeted therapeutic strategies, including TAM lipid metabolism inhibitors, dietary interventions, and combination therapies, are reviewed. Finally, clinical translation directions are proposed, emphasizing plasma metabolomic biomarkers, organ-specific metabolic heterogeneity, and spatial multi-omics research frameworks.