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.
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.
authors.affiliation: Ludwig Institute for Cancer Research Ltd., Lausanne Branch, University Hospital (CHUV), Hôpital Orthopédique Niv. 5, aile est, Av. Pierre Decker 4, 1011, Lausanne, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cesson
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Rivals
authors.forename: Anette
authors.initials: A
authors.lastname: Escher
authors.forename: Elsa
authors.initials: E
authors.lastname: Piotet
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Vilmos
authors.initials: V
authors.lastname: Posevitz
authors.forename: Danijel
authors.initials: D
authors.lastname: Dojcinovic
authors.forename: Philippe
authors.initials: P
authors.lastname: Monnier
authors.forename: Daniel
authors.initials: D
authors.lastname: Speiser
authors.forename: Luc
authors.initials: L
authors.lastname: Bron
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006682:HLA-DP Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments