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

Weide, Benjamin, Martens, Alexander, Zelba, Henning, Stutz, Christina, Derhovanessian, Evelyna, Di Giacomo, Anna Maria, Maio, Michele, Sucker, Antje, Schilling, Bastian, Schadendorf, Dirk, Büttner, Petra, Garbe, Claus, and Pawelec, Graham (2014) Myeloid-rerived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1-or Melan-A-specific T cells. Clinical Cancer Research, 20 (6). pp. 1601-1609.

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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.

Item ID: 33143
Item Type: Article (Research - C1)
ISSN: 1557-3265
Funders: Deutsche Forschungsgemeinschaft (DFG)
Projects and Grants: DFG grant SFB 685
Date Deposited: 14 May 2014 09:47
Downloads: Total: 5
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