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

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.

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  • 1Authors' Affiliations: Department of Dermatology, University Medical Center; Department of Internal Medicine II, Section for Transplantation Immunology and Immunohematology, University of Tübingen, Tübingen; German Cancer Research Center (DKFZ); German Cancer Consortium (DKTK), Heidelberg; Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany; Department of Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Italy; and Skin Cancer Research Group, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Australia.

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.

©2013 AACR.

PMID:
24323899
[PubMed - indexed for MEDLINE]
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