| Lipid-loaded tumor-associated macrophages are a subset of TAMs characterized by lipid droplet accumulation and lipid metabolic reprogramming in the tumor microenvironment, exhibiting marked tissue specificity and functional heterogeneity across different solid tumors. Their formation is closely associated with tumor-derived lipids, necrotic cell debris, extracellular vesicles, imbalanced lipid uptake and efflux, as well as microenvironmental cues such as hypoxia, lactate-driven acidification, and inflammatory cytokines. Current evidence indicates that lipid-loaded TAMs may promote tumor progression through metabolic support, immunosuppression, pro-angiogenic activity, extracellular matrix remodeling, and adaptation to therapeutic pressure, and may contribute to resistance to radiotherapy, chemotherapy, endocrine therapy, and immunotherapy. Targeting lipid metabolism-related pathways, in combination with immune checkpoint blockade, nanomedicine-based delivery, or cell-based therapy, provides potential strategies for remodeling the immunosuppressive tumor microenvironment. This review focuses on the conceptual definition, formation mechanisms, functional heterogeneity, and targeted therapeutic strategies of lipid-loaded tumor-associated macrophages, and discusses key challenges in their clinical translation. |
