Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells

Clin Cancer Res. 2014 Mar 15;20(6):1601-9. doi: 10.1158/1078-0432.CCR-13-2508. Epub 2013 Dec 9.


Purpose: To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared with functional tumor antigen-specific T cells in patients with melanoma with distant metastasis.

Experimental design: The percentage of CD14(+)CD11b(+)HLA-DR(-/low) MDSCs, CD4(+)CD25(+)FoxP3(+) Tregs, and the presence of NY-ESO-1- or Melan-A-specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan-Meier and log-rank tests. Multivariate analyses were performed using Cox regression models.

Results: NY-ESO-1-specific T cells, the M-category, and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1-specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of >11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months versus 8 months for others (P < 0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma antigen-specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs.

Conclusions: Circulating CD14(+)CD11b(+)HLA-DR(-/low) MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen-specific T cells in patients with advanced melanoma. Our findings provide a rationale to investigate MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance / immunology
  • Kaplan-Meier Estimate
  • MART-1 Antigen / immunology
  • Male
  • Melanoma / immunology*
  • Melanoma / mortality*
  • Membrane Proteins / immunology
  • Middle Aged
  • Myeloid Cells / immunology*
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Proteins