Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis

• Published in: Journal of clinical oncology Vol. 30; no. 15; pp. 1835 - 1841
• Main Authors: WEIDE, Benjamin, ZELBA, Henning, SCHADENDORF, Dirk, BIITTNER, Petra, GARBE, Claus, PAWELEC, Graham, DERHOVANESSIAN, Evelyna, PFLUGFELDER, Annette, EIGENTLER, Thomas K, DI GIACOMO, Anna Maria, MAIO, Michele, AARNTZEN, Erik H. J. G, DE VRIES, I. Jolanda M, SUCKER, Antje
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.05.2012
• Subjects: Antigens, Neoplasm - immunology; Biological and medical sciences; Cancer; Cell survival; Cohort Studies; Cytokines; Dermatology; Europe; Female; Humans; Immunotherapy; Inhibitor of Apoptosis Proteins - immunology; Kaplan-Meier Estimate; Lymphocytes T; MAGE-A3 antigen; Male; MART-1 Antigen - immunology; Medical sciences; Melanoma; Melanoma - immunology; Melanoma - mortality; Melanoma - secondary; Melanoma - therapy; Melanoma-associated antigen; Membrane Proteins - immunology; Metastases; Middle Aged; Neoplasm Proteins - immunology; NY-ESO-1 protein; Proportional Hazards Models; Regression analysis; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Skin Neoplasms - therapy; survivin; Survivors - statistics & numerical data; T-Lymphocytes - immunology; Time Factors; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Europe; Human; Cancerology; Tumor associated antigen; Targeting; T-Lymphocyte; Malignant melanoma; Malignant tumor; Metastasis; Survival; Cancer; NYESO1 antigen
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.40.2271

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. 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. 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. 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.