PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine.
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.
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital , Herlev, Denmark.
Shamaila
S
Munir Ahmad
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital , Herlev, Denmark.
Evelina
E
Martinenaite
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital , Herlev, Denmark.
Morten
M
Hansen
Department of Oncology, Copenhagen University Hospital , Herlev, Denmark.
Niels
N
Junker
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Troels Holz
TH
Borch
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Özcan
Ö
Met
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Marco
M
Donia
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Inge Marie
IM
Svane
Center for Cancer Immune Therapy (CCIT), Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Mads Hald
MH
Andersen
Anti-tregs; B7-H1; CD274; PD-L1; T cells; antigen; co-stimulation; dendritic cell-based vaccine; melanoma