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Metabolic targeting of HIV infection-induced myeloid-derived suppressor cells Amir Al-Khami, Paulo Rodriguez, Christopher Parsons, Augusto Ochoa Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans LA Myeloid-derived suppressor cells (MDSCs) accumulate in patients with cancer and chronic inflammatory diseases. We found that HIV-infected patients have increased numbers of circulating granulocytic MDSCs (G-MDSCs) that upregulate the major immunosuppressive pathways and inhibit T cell proliferation. MDSC numbers correlate with viral titers and are inversely proportional to CD4 T cell numbers, suggesting that G-MDSCs may play a role in the pathogenesis of the disease. We recently reported that tumor-associated MDSCs activate fatty acid oxidation (FAO) and, at the same time, upregulate their immunosuppressive mechanisms. Importantly, FAO inhibitors block MDSC function and induce a strong anti-tumor T cell response. The metabolic characteristics of G-MDSCs in HIV+ patients are unknown, and the potential role of FAO inhibition as a means of enhancing anti-retroviral therapy and reestablishing T cell function is unclear. Therefore, we hypothesize that “G-MDSCs in HIV+ patients increase FAO that supports the activation of their immunosuppressive mechanisms; FAO inhibition will block G-MDSC function and enhance T cell activity, thus potentiating the effect of anti-retroviral therapies”. To test this hypothesis, we plan to (1) determine the primary metabolic pathway used by G-MDSCs from HIV+ patients at different disease stages and establish its role in the activation of immunosuppressive mechanisms and (2) determine the effect of FAO inhibitors on G-MDSC function and HIV-specific T cell response. This study is funded in part by 1P30GM114732-01 to A. Ochoa (Pilot Project #2, A. Al-Khami).