High expression of ID1 in monocytes is strongly associated with phenotypic and functional MDSC markers in advanced melanoma.
Cancer Immunol Immunother
; 69(4): 513-522, 2020 Apr.
Article
en En
| MEDLINE
| ID: mdl-31953577
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
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Biomarcadores
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Proteína 1 Inhibidora de la Diferenciación
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Células Supresoras de Origen Mieloide
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Melanoma
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Aged80
/
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suecia