High Levels of Endogenous Omega-3 Fatty Acids Promote Dendritic Cell Antigen Presentation and Improve Dendritic Cell-Based Cancer Vaccine Efficacy in Mice.

Abstract

Antigen presentation by dendritic cells (DC) 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 levels of omega-3 fatty acids in mice significantly prolonged lifespan and reduced tumor growth and body weight loss. This effect was mediated in part by more effective DC antigen presentation. DCs derived from Tg(CAG-fat-1)Jxk/J transgenic mice expressing high omega-3 lipid levels were 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. Although no effect on the levels of expression of costimulatory molecules was detected, we discovered a marked enhancement of T-cell dwell time on DCs. We also observed that differentiating DCs from WT bone marrow in the presence of omega-3 lipids increased DC antigen presentation capacity in vitro, suggesting a potential approach to enhance DC-based cancer vaccine efficacy.