title: Generation of diverse mutated tumor antigen-specific cytotoxic T lymphocytes in a lung cancer patient with long survival.
abstract: We have identified an antigen recognized on a large cell carcinoma of the lung by tumor-specific cytotoxic T lymphocytes (CTL). The antigenic peptide is encoded by a mutated alpha-actinin-4 gene and presented by human leukocyte antigen (HLA)-A2. Using HLA-A2-peptide tetramers, we have derived from patient peripheral blood lymphocytes (PBL) and autologous tumor infiltrating lymphocytes (TIL) several mutated alpha-actinin-4-specific T cell clones. These clones displayed similar tetramer staining but distinct T cell receptor (TCR) usage and antitumor reactivity. Indeed, TIL clones lysed more efficiently the autologous tumor cells and released higher cytokine levels than PBL clones. Importantly, treatment of cancer cells with interferon-gamma enhanced their susceptibility to PBL clone-mediated lysis correlated with increase in HLA-class I expression. The present findings provide evidence that an immune T cell response took place in a lung cancer patient with favorable clinical evolution and suggest that CTL, recognizing a truly tumor-specific antigen, may contribute to controlling the tumor.
authors.affiliation: Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 INSERM, Institut Fédératif de Recherche-54, F-94 805 Villejuif, France.
authors.forename: Faten
authors.initials: F
authors.lastname: El Hage
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vergnon
authors.forename: Dominique
authors.initials: D
authors.lastname: Grunenwald
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Fathia
authors.initials: F
authors.lastname: Mami-Chouaib
mesh_terms: D000185:Actinin / Q000235:genetics* / Q000276:immunology; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D015789:HLA-A2 Antigen; D008840:Microfilament Proteins; D000185:Actinin