title: Accumulation of the p53 protein allows recognition by human CTL of a wild-type p53 epitope presented by breast carcinomas and melanomas.
abstract: The p53 protein is accumulated in tumor cells of many human cancers and can elicit in vivo humoral and proliferative responses. Rare reports about p53-mediated tumor recognition by CTLs have remained questioned. We therefore studied a panel of breast tumor and melanoma cell lines that we assayed for the presence of accumulated p53 and surface HLA-A2 and for the presentation of p53 epitopes. From PBMC of a healthy donor, we have generated a CTL line, D5/L9V, directed against HLA-A2-restricted peptide 264-272 from wild-type p53. It efficiently lysed breast adenocarcinomas MCF-7, MCF7/RA1, and MDA-MB-231, and melanoma M8, which all accumulate the p53 protein. Using competition assays, we made sure that tumor lysis by D5/L9V was due to recognition of endogenously produced p53 peptide 264-272 associated with the HLA-A2.1 molecule on the surface of these tumor cells. Cells with undetectable levels of wild-type p53, such as lymphoblastoid cells and melanoma M74, were not recognized by D5/L9V. Neither were breast tumor cell line MCF7/ADR nor melanoma line M44 because of HLA loss. This study therefore shows that it is possible to obtain in vitro CTL lines that specifically recognize a p53 epitope spontaneously presented by a variety of HLA-A2+ transformed cell lines provided they display abnormal patterns of p53 expression. This work points out that breast tumors and melanomas share a p53 epitope, and raises hopes for future immunotherapeutic approaches.
authors.affiliation: INSERM U445, Institut Cochin de Génétique Moléculaire, Université René Descartes Paris V, France. gnjatic@cochin.inserm.fr
authors.forename: S
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.forename: M
authors.initials: M
authors.lastname: Viguier
authors.forename: S
authors.initials: S
authors.lastname: Chouaib
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
authors.forename: J
authors.initials: J
authors.lastname: Choppin
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D010455:Peptides; D016159:Tumor Suppressor Protein p53