title: NY-ESO-1-specific circulating CD4+ T cells in ovarian cancer patients are prevalently T(H)1 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(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 1:25,000 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.
authors.forename: Nassima
authors.initials: N
authors.lastname: Redjimi
authors.forename: Karine
authors.initials: K
authors.lastname: Duperrier-Amouriaux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raimbaud
authors.forename: Immanuel
authors.initials: I
authors.lastname: Luescher
authors.forename: Danijel
authors.initials: D
authors.lastname: Dojcinovic
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Classe
authors.forename: Dominique
authors.initials: D
authors.lastname: Berton-Rigaud
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Frenel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bourbouloux
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000276:immunology / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D018655:Lymphocyte Count; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D008565:Membrane Proteins; D016753:Interleukin-10