TY  - JOUR
A1  - Wu, Hao
A1  - Han, Yijie
A1  - Rodriguez Sillke, Yasmina
A1  - Deng, Hongzhang
A1  - Siddiqui, Sophiya
A1  - Treese, Christoph
A1  - Schmidt, Franziska
A1  - Friedrich, Marie
A1  - Keye, Jacqueline
A1  - Wan, Jiajia
A1  - Qin, Yue
A1  - Kühl, Anja A.
A1  - Qin, Zhihai
A1  - Siegmund, Britta
A1  - Glauben, Rainer
T1  - Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages
JF  - EMBO molecular medicine
N2  - 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.
KW  - cancer immunotherapy
KW  - lipid droplets
KW  - lipid metabolism
KW  - tumor microenvironment
KW  - tumor-associated macrophage
Y1  - 2019
U6  - https://doi.org/10.15252/emmm.201910698
SN  - 1757-4676
SN  - 1757-4684
VL  - 11
IS  - 11
PB  - Wiley
CY  - Hoboken
ER  -