Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages

Abstract Tumor-associated macrophages (TAM) are important tumor-promoting cells. However, the mechanisms underlying how the tumor and its microenvironment reprogram these cells remain elusive. Here we report that lipids play a crucial role in generating TAMs in the tumor microenvironment (TME). Macrophages from both human and murine tumor tissues were enriched with lipids due to increased lipid uptake by macrophages. TAMs expressed elevated levels of the scavenger receptor CD36, accumulated lipids, and used fatty acid oxidation (FAO) instead of glycolysis for energy. High levels of FAO promoted mitochondrial oxidative phosphorylation, production of reactive oxygen species, phosphorylation of JAK1, and…

• CP
  Cancer Prevention and Research Institute of Texas

  Award: RR180044
• NI
  National Institutes of Health

  Awards: CA214811, CA211073, CA239255, R01s CA200539