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
Open Access
- 13 March 2014
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 20 (6), 1601-1609
- https://doi.org/10.1158/1078-0432.ccr-13-2508
Abstract
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. Clin Cancer Res; 20(6); 1601–9. ©2013 AACR.Keywords
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