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01-01-2011 | Original Article

MAGE-A3 and MAGE-A4 specific CD4⁺ T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes

Authors: Valérie Cesson, Jean-Paul Rivals, Anette Escher, Elsa Piotet, Kris Thielemans, Vilmos Posevitz, Danijel Dojcinovic, Philippe Monnier, Daniel Speiser, Luc Bron, Pedro Romero

Published in: Cancer Immunology, Immunotherapy | Issue 1/2011

Abstract

Frequent expression of cancer testis antigens (CTA) has been consistently observed in head and neck squamous cell carcinomas (HNSCC). For instance, in 52 HNSCC patients, MAGE-A3 and -A4 CTA were expressed in over 75% of tumors, regardless of the sites of primary tumors such as oral cavity or hypopharynx. Yet, T-cell responses against these CTA in tumor-bearing patients have not been investigated in detail. In this study, we assessed the naturally acquired T-cell response against MAGE-A3 and -A4 in nonvaccinated HNSCC patients. Autologous antigen-presenting cells pulsed with overlapping peptide pools were used to detect and isolate MAGE-A3 and MAGE-A4 specific CD4⁺ T cells from healthy donors and seven head and neck cancer patients. CD4⁺ T-cell clones were characterized by cytokine secretion. We could detect and isolate MAGE-A3 and MAGE-A4 specific CD4⁺ T cells from 7/7 cancer patients analyzed. Moreover, we identified six previously described and three new epitopes for MAGE-A3. Among them, the MAGE-A3_111–125 and MAGE-A3_161–175 epitopes were shown to be naturally processed and presented by DC in association with HLA-DP and DR, respectively. All of the detected MAGE-A4 responses were specific for new helper epitopes. These data suggest that naturally acquired CD4⁺ T-cell responses against CT antigens often occur in vivo in HNSCC cancer patients and provide a rationale for the development of active immunotherapeutic approaches in this type of tumor.

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Title: MAGE-A3 and MAGE-A4 specific CD4+ T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes
Authors: Valérie Cesson
Jean-Paul Rivals
Anette Escher
Elsa Piotet
Kris Thielemans
Vilmos Posevitz
Danijel Dojcinovic
Philippe Monnier
Daniel Speiser
Luc Bron
Pedro Romero
Publication date: 01-01-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 1/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0916-z

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