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.

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