title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Authors' 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.
authors: Benjamin
authors: B
authors: Weide
authors: Alexander
authors: A
authors: Martens
authors: Henning
authors: H
authors: Zelba
authors: Christina
authors: C
authors: Stutz
authors: Evelyna
authors: E
authors: Derhovanessian
authors: Anna Maria
authors: AM
authors: Di Giacomo
authors: Michele
authors: M
authors: Maio
authors: Antje
authors: A
authors: Sucker
authors: Bastian
authors: B
authors: Schilling
authors: Dirk
authors: D
authors: Schadendorf
authors: Petra
authors: P
authors: Büttner
authors: Claus
authors: C
authors: Garbe
authors: Graham
authors: G
authors: Pawelec
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D053208:Kaplan-Meier Estimate; D058965:MART-1 Antigen / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality*; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D011379:Prognosis; D016016:Proportional Hazards Models; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008565:Membrane Proteins