Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages
Hao Wu, Yijie Han, Yasmina Rodriguez Sillke, Hongzhang Deng, Sophiya Siddiqui, Christoph Treese, Franziska Schmidt, Marie Friedrich, Jacqueline Keye, Jiajia Wan, Yue Qin, Anja A Kühl, Zhihai Qin, Britta Siegmund
Abstract
Tumor‐associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs 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 TAMs 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.
附件下载：
Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages, EMBO Mol Med, 10 Oct 2019
EMBO Molecular Medicine, 10 October, 2019，DOI：https://doi.org/10.15252/emmm.201910698
Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages
Hao Wu, Yijie Han, Yasmina Rodriguez Sillke, Hongzhang Deng, Sophiya Siddiqui, Christoph Treese, Franziska Schmidt, Marie Friedrich, Jacqueline Keye, Jiajia Wan, Yue Qin, Anja A Kühl, Zhihai Qin, Britta Siegmund
Abstract
Tumor‐associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs 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 TAMs 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.
文章链接：https://www.embopress.org/doi/full/10.15252/emmm.201910698