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, Rainer Glauben
- 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.
MetadatenAuthor details: | Hao Wu, Yijie Han, Yasmina Rodriguez SillkeORCiD, Hongzhang DengORCiD, Sophiya Siddiqui, Christoph Treese, Franziska Schmidt, Marie FriedrichGND, Jacqueline Keye, Jiajia WanGND, Yue Qin, Anja A. KühlORCiDGND, Zhihai QinORCiD, Britta SiegmundORCiDGND, Rainer GlaubenGND |
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DOI: | https://doi.org/10.15252/emmm.201910698 |
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ISSN: | 1757-4676 |
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ISSN: | 1757-4684 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31602788 |
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Title of parent work (English): | EMBO molecular medicine |
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Publisher: | Wiley |
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Place of publishing: | Hoboken |
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Publication type: | Article |
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Language: | English |
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Year of first publication: | 2019 |
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Publication year: | 2019 |
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Release date: | 2020/10/06 |
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Tag: | cancer immunotherapy; lipid droplets; lipid metabolism; tumor microenvironment; tumor-associated macrophage |
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Volume: | 11 |
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Issue: | 11 |
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Number of pages: | 17 |
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Funding institution: | Helmholtz Alliance "Preclinical comprehensive cancer center" of the Helmholtz Society; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81630068/31670881, C0805/31600729]; Deutsche KrebshilfeDeutsche Krebshilfe [70112011]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [We5303-3-1]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation; China Scholarship CouncilChina Scholarship Council; "Fellowship for Young International Scientists"-program of the Chinese Academy of Science; German-Israeli Foundation for Scientific Research and DevelopmentGerman-Israeli Foundation for Scientific Research and Development [1295] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
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DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit |
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Peer review: | Referiert |
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Publishing method: | Open Access |
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| Open Access / Gold Open-Access |
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| DOAJ gelistet |
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