title: Rhabdomyosarcomas are potential target of MAGE-specific immunotherapies.
abstract: The search for alternative strategies of therapy remains a major issue for most neoplastic diseases. The expression of several tumor antigens makes human rhabdomyosarcomas, which are the most frequent form of soft tissue tumor in children, a good candidate for tumor-specific immunotherapy. To assess the feasibility of this approach, we evaluated the ability of rhabdomyosarcoma cell lines to process and present the MAGE-A tumor antigens to effectors of the immune system. To this end, we investigated recognition of MAGE-A-positive rhabdomyosarcoma cells by HLA-B*3701-restricted T cells specific for a MAGE-A-derived peptide. Low level of HLA expression impaired recognition of the tumor cells. Therefore, to obtain HLA expression avoiding the use of IFN-gamma and TNF-alpha, which could affect the proteasome activity, a rhabdomyosarcoma line was transduced by a retroviral vector encoding the HLA-B*3701 allele. Recognition of the infected cells was then observed also in the absence of IFN-gamma and TNF-alpha treatment, thus demonstrating that rhabdomyosarcoma cells were indeed able to naturally process and present the MAGE-A antigens. These results demonstrate that rhabdomyosarcoma cells expressing MAGE-A can be targets of tumor-specific effectors, suggesting the feasibility of clinical protocols of specific immunotherapy also for the treatment of rhabdomyosarcoma.
authors.affiliation: MolMed, via Olgettina 58, 20132 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tanzarella
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lionello
authors.forename: Barbara
authors.initials: B
authors.lastname: Valentinis
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Lollini
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D005240:Feasibility Studies; D015235:HLA-B Antigens / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015235:HLA-B Antigens; C072013:MAGEA3 protein, human; C420909:Mage-a2 antigen; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma