Weide, Benjamin, Zelba, Henning, Derhovanessian, Evelyna, Pflugfelder, Annette, Eigentler, Thomas K., Giacomo, Anna Maria Di, Maio, Michele, Aarntzen, Erik H.J.G., de Vries, I. Jolanda, Sucker, Antje, Schadendorf, Dirk, Büttner, Petra, Garbe, Claus, and Pawelec, Graham (2012) Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis. Journal of Clinical Oncology, 30 (15). pp. 1835-1841.

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Abstract

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.

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