MAGE-1 and MAGE-3 or -6 expression in neuroblastoma-related pediatric solid tumors.
MAGE-1 and MAGE-3 or -6 are genes encoding melanoma-rejection antigens recognized by cytotoxic T lymphocytes in an HLA-A1 restriction manner. MAGE-1 and MAGE-3 or -6 were expressed in 5/14 (36%) and 6/14 (43%) neuroblastoma (NB) cell lines, and in 20/41 (49%) and 24/41 (59%) clinical NB-related tumors, respectively. Additionally, they were also expressed in pediatric tumors of other types such as rhabdomyosarcoma and Wilms' tumor. MAGE-1 expression at a functional level in tumor cells was confirmed by the cytotoxicity assay using MAGE-1-specific tumor-infiltrating lymphocytes (TIL). In clinical NB-related tumors, MAGE-3 or -6 expression demonstrated an inverse correlation to clinical stage. Furthermore, although the sample number was small, the incidence of MAGE-1 and/or MAGE-3 or -6 expression was significantly correlated to the absence of metastasis and a more favorable clinical outcome (p < 0.05). These results may suggest that NB cells silent for the expression of MAGE genes escape from the host anti-tumor immune response and consequently retain a growth advantage. Finally, NB-related tumors could be reliable candidates for immunotherapy targeted towards MAGE gene products.
Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
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H
Ishida
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Matsumura
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ML
Salgaller
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Y
Ohmizono
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Kadono
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Sawada
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007223:Infant; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C095203:MAGEA6 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins