Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages
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 exemplifie...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2019-11-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201910698 |
| _version_ | 1797284293390630912 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hao Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T17:47:04Z |
| format | Article |
| id | doaj.art-8c67af085da04323ba732ea32b84e9f4 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:47:04Z |
| publishDate | 2019-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-8c67af085da04323ba732ea32b84e9f42024-03-02T14:52:43ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-11-011111n/an/a10.15252/emmm.201910698Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophagesHao Wu0Yijie Han1Yasmina Rodriguez Sillke2Hongzhang Deng3Sophiya Siddiqui4Christoph Treese5Franziska Schmidt6Marie Friedrich7Jacqueline Keye8Jiajia Wan9Yue Qin10Anja A Kühl11Zhihai Qin12Britta Siegmund13Rainer Glauben14The First Affiliated Hospital Zhengzhou University Zhengzhou ChinaUniversity of Chinese Academy of Sciences Beijing ChinaMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyDepartment of Polymer Science and Engineering Key Laboratory of Systems Bioengineering (Ministry of Education) School of Chemical Engineering and Technology Tianjin University Tianjin ChinaMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyThe First Affiliated Hospital Zhengzhou University Zhengzhou ChinaNational Center for Nanoscience and Technology Beijing ChinaiPATH.Berlin – Core Unit of the Charité Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyThe First Affiliated Hospital Zhengzhou University Zhengzhou ChinaMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyMedical Department for Gastroenterology Infectious Diseases and Rheumatology Charité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humboldt‐Universität zu Berlin, and Berlin Institute of Health Berlin GermanyAbstract 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.https://doi.org/10.15252/emmm.201910698cancer immunotherapylipid dropletslipid metabolismtumor microenvironmenttumor‐associated macrophage |
| spellingShingle | 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 Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages EMBO Molecular Medicine cancer immunotherapy lipid droplets lipid metabolism tumor microenvironment tumor‐associated macrophage |
| title | Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages |
| title_full | Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages |
| title_fullStr | Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages |
| title_full_unstemmed | Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages |
| title_short | Lipid droplet‐dependent fatty acid metabolism controls the immune suppressive phenotype of tumor‐associated macrophages |
| title_sort | lipid droplet dependent fatty acid metabolism controls the immune suppressive phenotype of tumor associated macrophages |
| topic | cancer immunotherapy lipid droplets lipid metabolism tumor microenvironment tumor‐associated macrophage |
| url | https://doi.org/10.15252/emmm.201910698 |
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