Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages

Pan Su, Qiang Wang, Enguang Bi, Xingzhe Ma, Lintao Liu, Maojie Yang, Jianfei Qian, Qing Yi

Research output: Contribution to journalArticle

3 Scopus citations

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 dephosphorylation of SHP1, leading to STAT6 activation and transcription of genes that regulate TAM generation and function. These processes were critical for TAM polarization and activity, both in vitro and in vivo. In summary, we highlight the importance of lipid metabolism in the differentiation and function of protumor TAMs in the TME.

Original languageEnglish (US)
Pages (from-to)1438-1450
Number of pages13
JournalCancer research
Volume80
Issue number7
DOIs
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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