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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

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

In: Cancer Immunology, Immunotherapy, 2011, vol. 60, no. 1, p. 23-35

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    Titre
    • 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
    Auteur
    • Cesson, Valérie. Ludwig Institute for Cancer Research Ltd., Lausanne Branch, University Hospital (CHUV), Hôpital Orthopédique Niv. 5, aile est, Av. Pierre Decker 4, 1011, Lausanne, Switzerland
    • Rivals, Jean-Paul. Service of Head and Neck Surgery, University Hospital, Lausanne, Switzerland
    • Escher, Anette. Service of Head and Neck Surgery, University Hospital, Lausanne, Switzerland
    • Piotet, Elsa. Service of Head and Neck Surgery, University Hospital, Lausanne, Switzerland
    • Thielemans, Kris. Department of Physiology-Immunology, Medical School of the Vrje Universiteit Brussel, Brussels, Belgium
    • Posevitz, Vilmos. Ludwig Institute for Cancer Research Ltd., Lausanne Branch, University Hospital (CHUV), Hôpital Orthopédique Niv. 5, aile est, Av. Pierre Decker 4, 1011, Lausanne, Switzerland
    • Dojcinovic, Danijel. Ludwig Institute for Cancer Research Ltd., Lausanne Branch, 1066, Epalinges, Switzerland
    • Monnier, Philippe. Service of Head and Neck Surgery, University Hospital, Lausanne, Switzerland
    • Speiser, Daniel. Ludwig Institute for Cancer Research Ltd., Lausanne Branch, University Hospital (CHUV), Hôpital Orthopédique Niv. 5, aile est, Av. Pierre Decker 4, 1011, Lausanne, Switzerland
    • Bron, Luc. Service of Head and Neck Surgery, University Hospital, Lausanne, Switzerland
    • Romero, Pedro. Ludwig Institute for Cancer Research Ltd., Lausanne Branch, University Hospital (CHUV), Hôpital Orthopédique Niv. 5, aile est, Av. Pierre Decker 4, 1011, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Cancer Immunology, Immunotherapy, 2011, vol. 60, no. 1, p. 23-35. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:311185
    Summary
    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-A3111-125 and MAGE-A3161-175 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