title: Human blood myeloid and plasmacytoid dendritic cells cross activate each other and synergize in inducing NK cell cytotoxicity.
abstract: Human blood dendritic cells (DCs) hold great potential for use in anticancer immunotherapies. CD1c+myeloid DCs and plasmacytoid DCs (pDCs) have been successfully utilized in clinical vaccination trials against melanoma. We hypothesize that combining both DC subsets in a single vaccine can further improve vaccine efficacy. Here, we have determined the potential synergy between the two subsetsin vitroon the level of maturation, cytokine expression, and effector cell induction. Toll-like receptor (TLR) stimulation of CD1c+DCs induced cross-activation of immature pDCs and vice versa. When both subsets were stimulated together using TLR agonists, CD86 expression on pDCs was increased and higher levels of interferon (IFN)-α were produced by DC co-cultures. Although the two subsets did not display any synergistic effect on naive CD4+and CD8+T cell polarization, CD1c+DCs and pDCs were able to complement each other's induction of other immune effector cells. The mere presence of pDCs in DC co-cultures promoted plasma cell differentiation from activated autologous B cells. Similarly, CD1c+DCs, alone or in co-cultures, induced high levels of IFN-γ from allogeneic peripheral blood lymphocytes or activated autologous natural killer (NK) cells. Both CD1c+DCs and pDCs could enhance NK cell cytotoxicity, and interestingly DC co-cultures further enhanced NK cell-mediated killing of an NK-resistant tumor cell line. These results indicate that co-application of human blood DC subsets could render DC-based anticancer vaccines more efficacious.
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, the Netherlands.
authors.forename: Jasper J P
authors.identifier: 0000-0001-5888-0125
authors.initials: JJ
authors.lastname: van Beek
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, the Netherlands.
authors.forename: Mark A J
authors.identifier: 0000-0003-3621-226X
authors.initials: MA
authors.lastname: Gorris
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annette E
authors.identifier: 0000-0002-5309-8860
authors.initials: AE
authors.lastname: Sköld
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, the Netherlands.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Hatipoglu
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences , Antwerp, Belgium.
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Van Acker
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.affiliation: Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, the Netherlands.
authors.forename: Ghaith
authors.initials: G
authors.lastname: Bakdash
keywords: Adaptive immunity; NK cells; cancer immunotherapy; crosstalk; myeloid DCs; plasmacytoid DCs