High expression of ID1 in monocytes is strongly associated with phenotypic and functional MDSC markers in advanced melanoma.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_E4C22A5DF32E
Type
Article: article from journal or magazin.
Collection
Publications
Title
High expression of ID1 in monocytes is strongly associated with phenotypic and functional MDSC markers in advanced melanoma.
Journal
Cancer immunology, immunotherapy
Author(s)
Melief J., Pico de Coaña Y., Maas R., Fennemann F.L., Wolodarski M., Hansson J., Kiessling R.
ISSN
1432-0851 (Electronic)
ISSN-L
0340-7004
Publication state
Published
Issued date
04/2020
Peer-reviewed
Oui
Volume
69
Number
4
Pages
513-522
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The efficacy of immunotherapies for malignant melanoma is severely hampered by local and systemic immunosuppression mediated by myeloid-derived suppressor cells (MDSC). Inhibitor of differentiation 1 (ID1) is a transcriptional regulator that was shown to be centrally involved in the induction of immunosuppressive properties in myeloid cells in mice, while it was overexpressed in CD11b <sup>+</sup> cells in the blood of late-stage melanoma patients. Therefore, we comprehensively assessed ID1 expression in PBMC from stage III and IV melanoma patients, and studied ID1 regulation in models for human monocyte differentiation towards monocyte-derived dendritic cells. A highly significant elevation of ID1 was observed in CD33 <sup>+</sup> CD11b <sup>+</sup> CD14 <sup>+</sup> HLA-DR <sup>low</sup> monocytic MDSC in the blood of melanoma patients compared to their HLA-DR <sup>high</sup> counterparts, while expression of ID1 correlated positively with established MDSC markers S100A8/9 and iNOS. Moreover, expression of ID1 in monocytes significantly decreased in PBMC samples taken after surgical removal of melanoma metastases, compared to those taken before surgery. Finally, maturation of monocyte-derived DC coincided with a significant downregulation of ID1. Together, these data indicate that increased ID1 expression is strongly associated with expression of phenotypic and immunosuppressive markers of monocytic MDSC, while downregulation is associated with a more immunogenic myeloid phenotype. As such, ID1 may be an additional phenotypic marker for monocytic MDSC. Investigation of ID1 as a pharmacodynamic biomarker or its use as a target for modulating MDSC is warranted.
Keywords
Adult, Aged, Aged, 80 and over, Animals, Biomarkers/metabolism, Cell Line, Tumor, Cells, Cultured, Female, HLA-DR Antigens/metabolism, Humans, Inhibitor of Differentiation Protein 1/metabolism, Male, Melanoma/blood, Melanoma/metabolism, Melanoma/surgery, Mice, Middle Aged, Monocytes/metabolism, Myeloid-Derived Suppressor Cells/metabolism, Phenotype, Cancer, Immunosuppression, Melanoma, Myeloid cells
Pubmed
Web of science
Open Access
Yes
Create date
23/01/2020 15:37
Last modification date
29/04/2021 15:37
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