Analysis of naturally acquired CD4+T-cell responses to MAGE-A3 and MAGE-A4 cancer/testis antigens in patients with resected head and neck squamous cell carcinoma

Details

Serval ID
serval:BIB_C02F7D2B93A4
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Title
Analysis of naturally acquired CD4+T-cell responses to MAGE-A3 and MAGE-A4 cancer/testis antigens in patients with resected head and neck squamous cell carcinoma
Title of the conference
Abstracts
Author(s)
Cesson V., Escher A., Piotet E., Rivals J. P., Speiser D., Bron L., Romero P.
ISBN
1424-7860
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
138
Series
Swiss Medical Weekly
Pages
53S-53S
Language
english
Abstract
Despite advances in the medical and surgical treatment of Head and Neck (HN) squamous cell carcinoma (HNSCC), long term survival has remained unchanged in the last 20 years. The obvious limitations of traditional therapeutic options strongly urge the development of novel therapeutic approaches. The molecular cloning of tumor antigens recognized by T lymphocytes in recent years has provided targets for specific immunotherapy. In this regard, frequent expression of Cancer Testis Antigens (CTA) has been repeatedly observed among HN tumors. We analyzed CTA expression in 46 HNSCC patients and found that MAGE-A3 and/or -A4 CTA were positive in over 70% of samples, regardless of the anatomical site of primary tumors in the upper aerodigestive tract. Still, immune responses against these CTA in HNSCC patients have not yet been investigated in detail. In this study we assessed the responsiveness of HNSCC patient's lymphocytes against overlapping peptides spanning the entire MAGE-A3 and -A4 proteins. After depletion of CD4+CD25+ regulatory T cells, and following three rounds of in vitro stimulation with pools of overlapping peptides, peripheral blood mononuclear cells (PBMCs) of HNSCC patients were screened by IFN-g and TNF-a intracellular cytokine staining for reactivity against MAGE-A3 or -A4 derived peptides. Cytokine secreting CD4+ T cells, specific for several peptides, were detected in 7/7 patients. In contrast, only 2/5 PBMC from healthy donors showed weak T cell responses against 2 peptides. CD4+ T cells specific for one epitope MAGE-A3(281-295), previously described as an HLA-DR11 restricted epitope naturally processed and presented by dendritic cells and tumor cells, were detected in two patients. MAGE-A3(161-175) specific CD4+ T cells were found in one patient. Six MAGE-A3 and -A4 new epitopes are being characterized. Together, these data suggest that naturally acquired CD4+ T cell responses against CT antigens occur in vivo in HNSCC patients, providing a rational basis for the use of the identified peptides in vaccination protocols.
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Create date
13/10/2009 14:22
Last modification date
20/08/2019 16:34
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