![]() In tumors, tumor-associated macrophages (TAMs) have been shown to regulate many critical processes associated with malignancy including promotion of tumor cell growth ( 2, 3), drug resistance ( 4– 6) and metastasis ( 7), induction of angiogenesis ( 8), and immune suppression ( 9, 10).Īlthough it is known that tumor and tumor microenvironment (TME) play an important role in polarizing MΦs into tumor-promoting TAMs ( 11), the underlying mechanisms remain partially elucidated. Heterogeneity of macrophages (MΦs) has long been recognized as the result of the plasticity and versatility of these cells to different microenvironmental stimuli ( 1). In summary, we highlight the importance of lipid metabolism in the differentiation and function of pro-tumor TAMs in the TME. These processes were critical for TAM polarization and activity both in vitro and in vivo. High levels of FAO promoted mitochondrial oxidative phosphorylation, production of reactive oxygen species, phosphorylation of JAK1 and dephosphorylation of SHP1, leading to STAT6 activation and transcription of genes that regulate TAM generation and function. TAMs expressed elevated levels of the scavenger receptor CD36, accumulated lipids, and used fatty acid oxidation (FAO) instead of glycolysis for energy. Macrophages from both human and murine tumor tissues were enriched with lipids due to increased lipid uptake by macrophages. Here we report that lipids play a crucial role in generating TAMs in the tumor microenvironment. However, the mechanisms underlying how the tumor and its microenvironment reprogram these cells remain elusive. Tumor-associated macrophages (TAMs) are important tumor-promoting cells. ![]()
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