Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis

J Clin Oncol. 2012 May 20;30(15):1835-41. doi: 10.1200/JCO.2011.40.2271. Epub 2012 Apr 23.


Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Cohort Studies
  • Europe
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / immunology
  • Kaplan-Meier Estimate
  • MART-1 Antigen / immunology*
  • Male
  • Melanoma* / immunology
  • Melanoma* / mortality
  • Melanoma* / secondary
  • Melanoma* / therapy
  • Membrane Proteins / immunology*
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Proportional Hazards Models
  • Skin Neoplasms* / immunology
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / therapy
  • Survivin
  • Survivors* / statistics & numerical data
  • T-Lymphocytes / immunology*
  • Time Factors
  • Treatment Outcome


  • Antigens, Neoplasm
  • BIRC5 protein, human
  • CTAG1B protein, human
  • Inhibitor of Apoptosis Proteins
  • MAGEA3 protein, human
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Survivin