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Oncoimmunology. 2016 Jul 1;5(8):e1202391. doi: 10.1080/2162402X.2016.1202391. eCollection 2016 Aug.

PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine.

Author information

1
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital , Herlev, Denmark.
2
Department of Oncology, Copenhagen University Hospital , Herlev, Denmark.
3
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
4
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

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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