Open AccessLipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages
Author(s) -
Wu Hao,
Han Yijie,
Rodriguez Sillke Yasmina,
Deng Hongzhang,
Siddiqui Sophiya,
Treese Christoph,
Schmidt Franziska,
Friedrich Marie,
Keye Jacqueline,
Wan Jiajia,
Qin Yue,
Kühl Anja A,
Qin Zhihai,
Siegmund Britta,
Glauben Rainer
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201910698
Subject(s) - immune system , phenotype , lipid metabolism , metabolism , fatty acid metabolism , macrophage , fatty acid , chemistry , immunology , biology , microbiology and biotechnology , biochemistry , gene , in vitro
Abstract Tumor‐associated macrophages ( TAM s) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAM s is controlled by long‐chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en‐route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAM s and tumor growth in vivo . In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate‐induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro‐tumoral myeloid cells on a metabolic level.