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

Cancer Immunol Immunother. 2020 Apr;69(4):513-522. doi: 10.1007/s00262-019-02476-9. Epub 2020 Jan 17.


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.

MeSH terms

  • 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


  • Biomarkers
  • HLA-DR Antigens
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1