High levels of endogenous Omega-3 Fatty Acids prolong the lifespan, promote antigen presentation, and improve DC-based cancer vaccine efficacy in mice

Antigen presentation by dendritic cells (DCs) is crucial in activating T-cells. DCs capture, process, and present antigens to T-cells, making them attractive vaccine vehicles. However, most DC cancer vaccines have had limited clinical efficacy, suggesting a need to increase their potency. We report that high omega-3 fatty acids in mice can significantly prolong lifespan and reduce tumor growth and body weight loss. This effect is mediated in part by more effective DC antigen presentation. DCs derived from Tg(CAG-fat-1)JxkJ (FAT-1) transgenic mice expressing high omega-3 lipid levels are better vaccine vehicles than wild-type (WT) DCs in treating cancers in WT mice and in stimulating CD8 T cell responses in vitro and in vivo. While no effect on costimulatory molecules was detected, we discovered a marked enhancement of T-cell dwell time on DCs. Differentiating DCs from bone marrow in the presence of omega-3 lipids can increase DC vaccine efficacy. Overall design: For the bulk RNAseq part of this study, we compared bone marrow, immature and mature BMDCs from FAT1 or WT mice (3 independent biological replicates per group).