title: Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis.
abstract: OBJECTIVE
  To analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis.
  
  
  METHODS
  We examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (> 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation.
  
  
  RESULTS
  In cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M category in predicting outcome. Median survival of patients possessing T cells responding to NY-ESO-1, Melan-A, or both was 21 months, compared with 6 months for all others. NY-ESO-1-responsive T cells were detected in 70% of cohort A patients surviving > 18 months and in 50% of cohort B patients. Melan-A responses were found in 42% and 47% of patients in cohorts A and B, respectively. In contrast, the proportion was only 22% for NY-ESO-1 and 23% for Melan-A in those who died within 6 months.
  
  
  CONCLUSIONS
  The presence of circulating T cells responding to Melan-A or NY-ESO-1 had strong independent prognostic impact on survival in advanced melanoma. Our findings support the therapeutic relevance of Melan-A and NY-ESO-1 as targets for immunotherapy.
authors.affiliation: University Medical Center, University of Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.forename: Henning
authors.initials: H
authors.lastname: Zelba
authors.forename: Evelyna
authors.initials: E
authors.lastname: Derhovanessian
authors.forename: Annette
authors.initials: A
authors.lastname: Pflugfelder
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Eigentler
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Petra
authors.initials: P
authors.lastname: Büttner
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology; D053208:Kaplan-Meier Estimate; D058965:MART-1 Antigen / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077022:Survivin; D017741:Survivors / Q000706:statistics & numerical data; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; C104948:CTAG1B protein, human; D051034:Inhibitor of Apoptosis Proteins; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000077022:Survivin