title: Recognition of pleural mesothelioma by mucin-1(950-958)/human leukocyte antigen A*0201-specific CD8+ T-cells.
abstract: Recent clinical investigations have demonstrated that T-cell-based immunotherapy of malignant pleural mesothelioma (MPM) could represent an alternative to the other therapeutic strategies. However, its development suffers from the lack of identified tumour antigenic targets. Mucin (MUC)1, which is expressed and recognised by cytotoxic T-cells in numerous cancer types, has not been investigated as a potential immune target in MPM. Thus, the objective of this study was to analyse MUC1 expression by MPM cells and to determine whether this antigen can be the target of cytotoxic CD8+ T-cells (cytotoxic T-lymphocytes (CTLs)). We first evaluated the expression and glycosylation of MUC1 by MPM cell lines using different MUC1-specific monoclonal antibodies. We then obtained a CTL clone specific for a MUC1 peptide (residues 950-958) presented by human leukocyte antigen (HLA)-A*0201 and studied its interferon-γ and cytotoxic response to MPM cell lines. We found that all MPM cell lines expressed MUC1 protein at the cell surface with different glycosylation profiles. We also observed that HLA-A*0201+ MPM cell lines are recognised and lysed by a HLA-A*0201/MUC1(950-958)-specific CTL clone independently of the MUC1 glycosylation profile. Thus, MUC1 expression and antigen presentation by MPM cells may represent an attractive target for immunotherapeutic treatment of MPM despite its hyperglycosylated profile.
authors.affiliation: INSERM, U892 Institut de Recherche Thérapeutique, Université de Nantes, Nantes Cedex 1, France.
authors.forename: D
authors.initials: D
authors.lastname: Roulois
authors.forename: V
authors.initials: V
authors.lastname: Vignard
authors.forename: F
authors.initials: F
authors.lastname: Gueugnon
authors.forename: N
authors.initials: N
authors.lastname: Labarrière
authors.forename: M
authors.initials: M
authors.lastname: Grégoire
authors.forename: J-F
authors.initials: JF
authors.lastname: Fonteneau
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002999:Clone Cells; D006031:Glycosylation; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000276:immunology*; D018396:Mucin-1 / Q000276:immunology / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018396:Mucin-1