Tiwary et al. focused on improving dendritic cell (DC) cancer vaccine effectiveness using a transgenic mouse model (FAT-1) generating high omega-3/omega-6 lipid ratios. FAT-1 BM-derived DCs were more efficient antigen-presenting cells in vitro, compared to WT. A FAT-1-derived DC vaccine was superior in stimulating CD8+ T cell responses in vitro and in vivo, and significantly reduced tumor burden and prolonged survival in several models. RNAseq revealed that T cells interacted with FAT-1 BMDCs for a significantly longer duration (>10-fold). Also, adding omega-3 lipids during in vitro differentiation of DCs from WT BM increased their antigen presentation capacity.
Contributed by Katherine Turner
ABSTRACT: 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.
Author Info: (1) National Cancer Institute, Bethesda, United States. (2) National Cancer Institute, Bethesda, United States. (3) Frederick National Laboratory for Cancer Research, Frederick, MD
Author Info: (1) National Cancer Institute, Bethesda, United States. (2) National Cancer Institute, Bethesda, United States. (3) Frederick National Laboratory for Cancer Research, Frederick, MD, United States. (4) NCI, NIH, Bethesda, MD, United States. (5) National Cancer Institute, Bethesda, MD, United States.
