Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages.,EMBO Molecular Medicine

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Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages.
EMBO Molecular Medicine ( IF 9.0 ) Pub Date : 2019-10-10 , DOI: 10.15252/emmm.201910698
Hao Wu _{1,

2,

3,

4} , Yijie Han ₅ , Yasmina Rodriguez Sillke _{2,

3,

6} , Hongzhang Deng ₇ , Sophiya Siddiqui _{2,

3,

4} , Christoph Treese _{2,

3,

8} , Franziska Schmidt _{2,

3,

4} , Marie Friedrich _{2,

3,

4} , Jacqueline Keye _{2,

3,

4} , Jiajia Wan ₁ , Yue Qin ₉ , Anja A Kühl _{2,

10} , Zhihai Qin ₁ , Britta Siegmund _{2,

3} , Rainer Glauben _{2,

3}

Affiliation

The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Corporate Member of Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Medical Department for Gastroenterology, Infectious Diseases and Rheumatology, Berlin Institute of Health, Berlin, Germany.
Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Berlin, Germany.
Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
Department of Polymer Science and Engineering, Key Laboratory of Systems, Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Berlin Institute of Health (BIH), Berlin, Germany.
National Center for Nanoscience and Technology, Beijing, China.
iPATH.Berlin - Core Unit of the Charité, Berlin Institute of Health, Berlin, Germany.

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.

中文翻译：

脂质液滴依赖性脂肪酸代谢控制肿瘤相关巨噬细胞的免疫抑制表型。

肿瘤相关巨噬细胞（TAM）通过抑制肿瘤免疫监视来促进肿瘤生长和转移。在本文中，我们提供证据表明，TAMs的免疫抑制表型受长链脂肪酸代谢（特别是不饱和脂肪酸）控制，此处以油酸酯为例。因此，在途中富集的脂滴被鉴定为必需的细胞器，代表化学抑制剂有效阻断TAM的体外极化和体内肿瘤生长的有效靶标。一致地，对人类肿瘤的分析表明，浸润结肠癌但未浸润胃癌组织的髓样细胞确实积聚了脂质液滴。从机理上讲，我们的数据表明油酸盐诱导的髓样细胞极化取决于雷帕霉素途径的哺乳动物靶标。因此，

更新日期：2019-11-07

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