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Spontaneous CD4 +  T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4 +  T cells in EOC patients with spontaneous immune responses to the antigen are prevalently T H 1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer +  cells  ex vivo , at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer +  cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25 + FOXP3 + Treg. Thus, spontaneous CD4 +  T-cell responses to ESO in cancer patients are prevalently of T H 1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines.

NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment