MAGE-1 andMAGE-3 or-6 expression in neuroblastoma-related pediatric solid tumors

Abstract

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.