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Cancer Immunol Immunother. 2020 Jan 17. doi: 10.1007/s00262-019-02476-9. [Epub ahead of print]

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

Author information

1
Department of Oncology-Pathology, Karolinska Institute, Visionsgatan 4, 171 64 Solna, Stockholm, Sweden. jeroen.melief@ki.se.
2
Department of Oncology-Pathology, Karolinska Institute, Visionsgatan 4, 171 64 Solna, Stockholm, Sweden.
3
Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
4
Department of Tumor Immunology, Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Karolinska University Hospital Solna, Stockholm, Sweden.

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+ 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+CD11b+CD14+HLA-DRlow monocytic MDSC in the blood of melanoma patients compared to their HLA-DRhigh 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:

Cancer; Immunosuppression; Melanoma; Myeloid cells

PMID:
31953577
DOI:
10.1007/s00262-019-02476-9

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