PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine
Shamaila Munir Ahmad, Evelina Martinenaite, Morten Hansen, Niels Junker, Troels Holz Borch, Özcan Met, Marco Donia, Inge Marie Svane, Mads Hald Andersen, Shamaila Munir Ahmad, Evelina Martinenaite, Morten Hansen, Niels Junker, Troels Holz Borch, Özcan Met, Marco Donia, Inge Marie Svane, Mads Hald Andersen
Abstract
We recently described naturally occurring PD-L1-specific T cells that recognize PD-L1-expressing immune cells as well as malignant cells. In the present study, we investigated whether the immunogenicity of a dendritic cell (DC)-based vaccine could be influenced by co-stimulation with a known PD-L1-derived epitope. We incubated a PD-L1-derived peptide epitope (19 amino acids long) or a control peptide (an irrelevant HIV epitope) with peripheral blood mononuclear cells from patients with malignant melanoma who had received a DC-based vaccine. We observed a significantly higher number of T cells that reacted to the vaccine in cultures that had been co-stimulated with the PD-L1 peptide epitope compared to cultures incubated with control peptide. Next, we characterized a novel PD-L1-derived epitope (23 amino acids long) and found that co-stimulation with both PD-L1 epitopes boosted the immune response elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents.
Keywords: Anti-tregs; B7-H1; CD274; PD-L1; T cells; antigen; co-stimulation; dendritic cell-based vaccine; melanoma.
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Source: PubMed