Tu128 - Enhanced Function of Vaccine Dendritic Cells from Obese Donor upon Inhibition of Lipid Metabolism

In the last decade tumor immunotherapy has been revolutionized by the implementation of checkpoint inhibitors that “remove the brake” posed by the tumor microenvironment onto the immune system. There exists increasing evidence that for optimal patients´ outcome an active vaccination to “start the engine” of the immune response is also needed. For this reason, it is important to optimize the protocol for the production of dendritic cells (DC)-based vaccines. In light of the link found between metabolism and function of immune cells, we focused on the manipulation of metabolic pathways during the in vitro differentiation process and implemented monocytes from obese donors, a population for which impaired immune response as well as enhanced risk for cancer development have been reported. Treatment of monocytes with different inhibitors of lipid metabolism resulted in mature DC with a lower expression of costimulatory molecules on their surface, but with an enhanced capability to induce the cytotoxic activity and IFNγ secretion of autologous effector cells. Mechanistically, the inhibition of the lipid metabolism drastically reduced the otherwise high levels of IL-10 secretion by obese mature DC leading to enhanced IL-12p70 to IL10 ratio and type1 polarization of the immune response.  Thus, an enhanced immune function can be obtained in obese patients by treating their DC with a” lipid diet” during the in vitro protocol for their production.