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
Identifieur interne : 002705 ( Main/Exploration ); précédent : 002704; suivant : 002706MAGE-A3 and MAGE-A4 specific CD4+ T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes
Auteurs : Valérie Cesson [Suisse] ; Jean-Paul Rivals [Suisse] ; Anette Escher [Suisse] ; Elsa Piotet [Suisse] ; Kris Thielemans [Belgique] ; Vilmos Posevitz [Suisse] ; Danijel Dojcinovic [Suisse] ; Philippe Monnier [Suisse] ; Daniel Speiser [Suisse] ; Luc Bron [Suisse] ; Pedro Romero [Suisse]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2011-01-01.
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Abstract
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-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.
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DOI: 10.1007/s00262-010-0916-z
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Pierre Decker 4, 1011, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Suisse</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Cancer Immunology, Immunotherapy</title><title level="j" type="abbrev">Cancer Immunol Immunother</title><idno type="ISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2011-01-01">2011-01-01</date><biblScope unit="volume">60</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="23">23</biblScope><biblScope unit="page" to="35">35</biblScope></imprint><idno type="ISSN">0340-7004</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-7004</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CD4+ T cells</term><term>HNSCC</term><term>MAGE-A3</term><term>MAGE-A4</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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-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.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>Suisse</li></country><region><li>Canton de Vaud</li><li>Région de Bruxelles-Capitale</li></region><settlement><li>Bruxelles</li><li>Lausanne</li></settlement></list><tree><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Cesson, Valerie" sort="Cesson, Valerie" uniqKey="Cesson V" first="Valérie" last="Cesson">Valérie Cesson</name></region><name sortKey="Bron, Luc" sort="Bron, Luc" uniqKey="Bron L" first="Luc" last="Bron">Luc Bron</name><name sortKey="Dojcinovic, Danijel" sort="Dojcinovic, Danijel" uniqKey="Dojcinovic D" first="Danijel" last="Dojcinovic">Danijel Dojcinovic</name><name sortKey="Escher, Anette" sort="Escher, Anette" uniqKey="Escher A" first="Anette" last="Escher">Anette Escher</name><name sortKey="Monnier, Philippe" sort="Monnier, Philippe" uniqKey="Monnier P" first="Philippe" last="Monnier">Philippe Monnier</name><name sortKey="Piotet, Elsa" sort="Piotet, Elsa" uniqKey="Piotet E" first="Elsa" last="Piotet">Elsa Piotet</name><name sortKey="Posevitz, Vilmos" sort="Posevitz, Vilmos" uniqKey="Posevitz V" first="Vilmos" last="Posevitz">Vilmos Posevitz</name><name sortKey="Rivals, Jean Paul" sort="Rivals, Jean Paul" uniqKey="Rivals J" first="Jean-Paul" last="Rivals">Jean-Paul Rivals</name><name sortKey="Romero, Pedro" sort="Romero, Pedro" uniqKey="Romero P" first="Pedro" last="Romero">Pedro Romero</name><name sortKey="Romero, Pedro" sort="Romero, Pedro" uniqKey="Romero P" first="Pedro" last="Romero">Pedro Romero</name><name sortKey="Speiser, Daniel" sort="Speiser, Daniel" uniqKey="Speiser D" first="Daniel" last="Speiser">Daniel Speiser</name></country><country name="Belgique"><region name="Région de Bruxelles-Capitale"><name sortKey="Thielemans, Kris" sort="Thielemans, Kris" uniqKey="Thielemans K" first="Kris" last="Thielemans">Kris Thielemans</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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