Antigen-specific T cells predict survival in patients with distant melanoma metastasis.
Major finding: Antigen-specific T cells predict survival in patients with distant melanoma metastasis.
Approach: Circulating functional T cells were analyzed from patients and survivors.
Impact: Vaccines and immunotherapies should target NY-ESO-1 and Melan-A.
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.