title: Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma.
abstract: HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER-family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family.
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.|Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.|Cancer Immunology, Inflammation and Tolerance Program, Georgia Regents University Cancer Center, Augusta, GA.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kumai
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oikawa
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Aoki
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Cancer Immunology, Inflammation and Tolerance Program, Georgia Regents University Cancer Center, Augusta, GA.
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.affiliation: Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D020893:Receptor, ErbB-3