Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines.
The tumor microenvironment is characterized by regulatory T cells, type II macrophages, myeloid-derived suppressor cells, and other immunosuppressive cells that promote malignant progression. Here we report the identification of a novel BDCA1(+)CD14(+) population of immunosuppressive myeloid cells that are expanded in melanoma patients and are present in dendritic cell-based vaccines, where they suppress CD4(+) T cells in an antigen-specific manner. Mechanistic investigations showed that BDCA1(+)CD14(+) cells expressed high levels of the immune checkpoint molecule PD-L1 to hinder T-cell proliferation. While this BDCA1(+)CD14(+) cell population expressed markers of both BDCA1(+) dendritic cells and monocytes, analyses of function, transcriptome, and proteome established their unique nature as exploited by tumors for immune escape. We propose that targeting these cells may improve the efficacy of cancer immunotherapy. Cancer Res; 76(15); 4332-46. ©2016 AACR.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Ghaith
G
Bakdash
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Sonja I
SI
Buschow
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Mark A J
MA
Gorris
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
Altuna
A
Halilovic
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Stanleyson V
SV
Hato
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Oncology and Pathology, Karolinska University Hospital Solna, Karolinska Institute, Stockholm, Sweden.
Annette E
AE
Sköld
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Gerty
G
Schreibelt
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Simone P
SP
Sittig
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Ruurd
R
Torensma
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Tjitske
T
Duiveman-de Boer
Sciomics GmbH, Heidelberg, Germany. Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
Christoph
C
Schröder
Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. Center for Oncological Research, University of Antwerp, Antwerp, Belgium.
Evelien L
EL
Smits
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Carl G
CG
Figdor
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. Jolanda.deVries@radboudumc.nl.
I Jolanda M
IJ
de Vries
D019496:Cancer Vaccines / Q000235:genetics*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D059016:Tumor Microenvironment
D019496:Cancer Vaccines; D018950:Lipopolysaccharide Receptors