期刊
EMBO MOLECULAR MEDICINE
卷 11, 期 11, 页码 -出版社
WILEY
DOI: 10.15252/emmm.201910698
关键词
cancer immunotherapy; lipid droplets; lipid metabolism; tumor microenvironment; tumor-associated macrophage
资金
- Helmholtz Alliance Preclinical comprehensive cancer center of the Helmholtz Society
- National Natural Science Foundation of China [C0805/31600729, 81630068/31670881]
- Deutsche Krebshilfe [70112011]
- Deutsche Forschungsgemeinschaft [We5303-3-1]
- China Postdoctoral Science Foundation
- China Scholarship Council
- Fellowship for Young International Scientists-program of the Chinese Academy of Science
- German-Israeli Foundation for Scientific Research and Development [1295]
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.
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