Lipid Metabolism Reprogramming in Tumor-Associated Macrophages Modulates Their Function in Primary Liver Cancers

Lipids are a complex class of biomolecules with pivotal roles in the onset, pro- gression, and maintenance of cancers. Lipids, derived from the tumor microenvironment (TME) or synthesized by cancer cells themselves, govern a large variety of pro-tumor- igenic functions. In recent years, lipid metabolism and the reprogramming of liver cancer cells have received increasing attention, revealing that altered regulation of diverse lipid species, including triacylglycerols, phospholipids, sphingolipids, ceramides, fatty acids, and cholesterol, actively contributes to the initiation and progression of primary liver can- cer. Lipid metabolic reprogramming also modifies the TME by influencing the recruit- ment, activation, and function of immune cells. Tumor-associated macrophages (TAM) are essential components of TME that sustain cancer growth, promoting invasion and me- diating immune evasion. Macrophage polarization toward a tumor-supportive pheno- type is associated with metabolic reprogramming. Indeed, lipid accumulation and en- hanced fatty acid oxidation in TAM contribute to polarization to a M2 phenotype. In this review, we examine lipid metabolism in hepatocellular carcinoma and cholangiocarci- noma, focusing on TAM lipid metabolic reprogramming.