title: The tumor antigens RHAMM and G250/CAIX are expressed in head and neck squamous cell carcinomas and elicit specific CD8+ T cell responses.
abstract: Despite advances in surgery, radio- and chemotherapy, therapeutic approaches for patients with head and neck squamous carcinoma (HNSCC) need to be improved. Immunotherapies eliciting tumor specific immune responses might constitute novel treatment options. We therefore investigated the expression and immunogenicity of two tumor-associated antigens (TAA) the receptor for hyaluronic acid mediated motility (RHAMM) and carboanhydrase IX (G250/CAIX) in HNSCC patients. Twenty-two HNSCC samples were examined for the expression of RHAMM and G250 by Western blotting and immunohistochemistry, 14/22 samples were tested for HLA-A2 expression by flow cytometry. For 8/22 samples single tumor-cell suspensions were generated, and mixed lymphocyte peptide cultures (MLPC) were performed to evaluate the frequencies of cytotoxic T cells specifically recognizing RHAMM and G250 using Tetramer staining/multi-color flow cytometry and enzyme linked immunosorbent spot (ELISPOT) assays. RHAMM and G250 were expressed in 73 and 80% of the HNSCC samples at the protein level. A co-expression of both TAAs could be detected in 60% of the patients. In 4/8 HLA-A2+ patients, 0.06-0.13% of CD8+ effector T cells recognized Tetramers for RHAMM or G250 and secreted IFNgamma and granzyme B in ELISPOT assays. RHAMM and G250 are expressed at high frequency and high protein level in HNSCCs and are recognized by cytotoxic CD8+ effector T cells. Therefore both TAAs constitute interesting targets for T cell based immunotherapies for HNSCC.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
authors.forename: Eva
authors.initials: E
authors.lastname: Beyer
authors.forename: Franziska
authors.initials: F
authors.lastname: Borchert
authors.forename: Markus
authors.initials: M
authors.lastname: Rojewski
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Silke
authors.initials: S
authors.lastname: Gronau
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Herbert
authors.initials: H
authors.lastname: Riechelmann
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015789:HLA-A2 Antigen / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000276:immunology; D007150:Immunohistochemistry; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000951:Antigens, Neoplasm; D016326:Extracellular Matrix Proteins; D015789:HLA-A2 Antigen; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases