Expansion of a BDCA1+CD14+ Myeloid Cell Population in Melanoma Patients May Attenuate the Efficacy of Dendritic Cell Vaccines
Publication year
2016Source
Cancer Research, 76, 15, (2016), pp. 4332-46ISSN
Publication type
Article / Letter to editor
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Organization
Tumorimmunology
Pathology
Medical Oncology
Journal title
Cancer Research
Volume
vol. 76
Issue
iss. 15
Page start
p. 4332
Page end
p. 46
Subject
Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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. (c)2016 AACR.
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- Academic publications [238430]
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- Faculty of Medical Sciences [90359]
- Open Access publications [97507]
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