title: MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas.
abstract: Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.
authors.affiliation: Laboratory of Tumor Immunology, URA 1484 CNRS, University of Rene Descartes, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Housseau
authors.forename: D
authors.initials: D
authors.lastname: Zeliszewski
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: V
authors.initials: V
authors.lastname: Paradis
authors.forename: S
authors.initials: S
authors.lastname: Richon
authors.forename: A
authors.initials: A
authors.lastname: Ricour
authors.forename: J
authors.initials: J
authors.lastname: Bougaran
authors.forename: D
authors.initials: D
authors.lastname: Prapotnich
authors.forename: G
authors.initials: G
authors.lastname: Vallancien
authors.forename: G
authors.initials: G
authors.lastname: Benoit
authors.forename: L
authors.initials: L
authors.lastname: Desportes
authors.forename: P
authors.initials: P
authors.lastname: Bedossa
authors.forename: T
authors.initials: T
authors.lastname: Hercend
authors.forename: J M
authors.initials: JM
authors.lastname: Bidart
authors.forename: D
authors.initials: D
authors.lastname: Bellet
mesh_terms: D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology; D014571:Urologic Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D017252:CD3 Complex; D006680:HLA Antigens