T Cells Targeting NY-ESO-1 and Melan-A Are Prognostic in Melanoma

The prognosis of melanoma with unresectable distant metastasis remains very poor. Although serum biomarkers of melanoma origin have been investigated, none has proved uniformly successful in predicting outcome. T cells specific for melanoma-associated antigens also have been detected in the peripheral blood of patients with melanoma, but whether they can serve as immune system–based prognostic markers remains unknown. In a recent article, Weide and colleagues demonstrate that functional circulating T cells that respond to various tumor-associated antigens have prognostic significance in patients with distant melanoma metastasis. The authors analyzed the presence of circulating T cells reactive to 2 melanoma-specific antigens, MAGE-3 and Melan-A, and 2 nonspecific tumor antigens, NY-ESO-1 and survivin, in 84 patients, 18 long-term survivors, and 14 healthy controls. The presence of T cells reactive to NY-ESO-1 and/or Melan-A was independently associated with an increase in median overall survival from 6 to 21 months in patients with distant melanoma metastasis. In accordance with this observation, T cells specific for NY-ESO-1 and Melan-A, respectively, were detected in 70% and 42% of patients with active disease who survived greater than 18 months from the time of analysis and in 50% and 47% of long-term survivors. Patients who died within 6 months had background levels of these cells. Together, these findings suggest that functional T-cell responses can develop spontaneously and influence prognosis in patients with melanoma. Because NY-ESO-1- and Melan-A-specific T cells are associated with improved survival, vaccines and immunotherapies should selectively target these antigens.

Weide B, Zelba H, Derhovanessian E, Pflugfelder A, Eigentler TK, Di Giacomo AM, et al. Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis. J Clin Oncol 2012 Apr 23 [Epub ahead of print].