NY-ESO-1-Specific circulating CD4 + T cells in ovarian cancer patients are prevalently T H1 type cells undetectable in the CD25 +FOXP3 +Treg compartment

Abstract

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 H1 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 H1 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. © 2011 Redjimi et al.