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

Autor: Weide B; University Medical Center, University of Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de, Zelba H, Derhovanessian E, Pflugfelder A, Eigentler TK, Di Giacomo AM, Maio M, Aarntzen EH, de Vries IJ, Sucker A, Schadendorf D, Büttner P, Garbe C, Pawelec G
Jazyk: angličtina
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2012 May 20; Vol. 30 (15), pp. 1835-41. Date of Electronic Publication: 2012 Apr 23.
DOI: 10.1200/JCO.2011.40.2271
Abstrakt: 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.
Databáze: MEDLINE