Myeloid-derived suppressor cells (MDSC) play a major role in the immune defects associated with cancer. Although several mechanisms have been suggested as critical for MDSC-induced T cell suppression, there are no current therapies to block the accumulation and/or function of MDSC. Recent studies have highlighted the role of specific energy metabolic pathways in the activation and function of immune cells. However, the metabolic programs of tumor-associated MDSC (T-MDSC) remain unknown. Herein, we found that T-MDSC, but not splenic MDSC or normal myeloid cells, activated fatty acid oxidation (FAO). T-MDSC increased mitochondrial mass and function, key FAO enzymes, and oxygen consumption rate. Of interest, Inhibition of FAO blocked the immunosuppressive mechanisms and functions in T-MDSC and decreased their production of immunosuppressive cytokines. FAO inhibition also resulted in a T cell-dependent decrease in tumor growth and synergized with low-dose chemotherapy and cellular immunotherapy. Furthermore, targeting fatty acid uptake decreased the regulatory activity of T-MDSC. Human MDSC exhibited similar metabolic characteristics. These data support the possibility of targeting fatty acid metabolism as a novel approach to block MDSC and enhance cancer therapy.

Citation Format: Amir A. Al-Khami, Fokhrul Hossain, Dorota Wyczechowska, Liqin Zheng, Paulo Rodriguez, Augusto C. Ochoa. Targeting fatty acid metabolism regulates the immunosuppressive activity of myeloid-derived suppressor cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-271.

©2016 American Association for Cancer Research.
2016
American Association for Cancer Research.