Lipid Metabolism Reprogramming of Tumor-Associated Macrophages in the Tumor Microenvironment

Abstract

Lipid metabolic reprogramming drives the pro-tumorigenic function of tumor-associated macrophages (TAMs) within the tumor microenvironment. Moving beyond the classical M1/M2 dichotomy, this review categorizes TAMs into functionally distinct lipid-associated subsets, each defined by unique metabolic dependencies. Specific lipid-derived metabolites act as instructive signaling molecules that directly orchestrate TAM polarization toward immunosuppression. Key pathways governing lipid uptake, de novo lipogenesis, fatty acid oxidation, and transcriptional control represent actionable therapeutic targets. Reprogramming TAM lipid metabolism offers a promising strategy to overcome immunotherapy resistance, enhance anti-tumor immunity, and improve cancer treatment outcomes. By integrating recent advances in single-cell technologies and preclinical models, this review provides a comprehensive framework for understanding lipid reprogramming as a central driver of TAM function and highlights new directions for precision metabolic immunotherapy.