1. 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.
- Author
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Redjimi N, Duperrier-Amouriaux K, Raimbaud I, Luescher I, Dojcinovic D, Classe JM, Berton-Rigaud D, Frenel JS, Bourbouloux E, Valmori D, and Ayyoub M
- Subjects
- Adenocarcinoma, Clear Cell immunology, Adenocarcinoma, Clear Cell metabolism, Adenocarcinoma, Mucinous immunology, Adenocarcinoma, Mucinous metabolism, Adult, Aged, Antigens, Neoplasm metabolism, CD4-Positive T-Lymphocytes metabolism, Cystadenocarcinoma, Serous immunology, Cystadenocarcinoma, Serous metabolism, Female, Humans, Interleukin-10 metabolism, Interleukin-17 metabolism, Lymphocyte Count, Major Histocompatibility Complex, Membrane Proteins metabolism, Middle Aged, Ovarian Neoplasms metabolism, T-Lymphocytes, Regulatory metabolism, Th1 Cells metabolism, Antigens, Neoplasm immunology, CD4-Positive T-Lymphocytes immunology, Forkhead Transcription Factors metabolism, Interleukin-2 Receptor alpha Subunit metabolism, Membrane Proteins immunology, Ovarian Neoplasms immunology, T-Lymphocytes, Regulatory immunology, Th1 Cells immunology
- 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.
- Published
- 2011
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