摘要
Background:Melanoma-associated antigen(Mage)-d4 was originally identified as a glioma-specific antigen.This study aimed to investigate the expression of Mage-d4 and its roles in tumorigenesis and cellular immune response to determine its potential as a prognosis and immunotherapeutic target for glioma.Methods:Mage-d4 expression was evaluated by immunohistochemistry(IHC) in 124 glioma specimens,among which were 84 patients followed up.To investigate the biological role of Mage-d4 in tumorigenesis,its expression was up-or down-regulated in glioma cell lines A172 and U251,followed by ts phenotypic effects were evaluated in vitro.For cellular immune response,human monocyte-derived dendritic cells(DCs) loaded with Mage-d4 recombinant protein,was used to stimulate in vitro to generate Maged4-specific cytotoxic T lymphocytes(CTLs) as demonstrated by IFN-γ production and cytotoxicity against glioma cells.Results:Mage-d4 protein was observed in 97 out of 124(78.2%) of glioma tissues tested.Furthermore,it was found to positively correlate with WHO grade and to be an independent prognostic factor for poor outcome.Down-regulation of Mage-d4 expression in U251 significantly suppressed cell growth,migration and invasion.On the contrary,these malignant behaviors were enhanced by up-regulation of Mage-d4 expression in A172.IFN-γ-producing Maged4-specific CTLs lysed Maged4-expressing HLA-A2+ U251 instead of Maged4-expressing HLA-A2-A172 in dose-dependent and HLA-A2-restricted manners.Conclusion:Our findings suggest that Mage-d4 overexpression contributes to the tumorigenesis of glioma cells and may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in glioma.
Background:Melanoma-associated antigen(Mage)-d4 was originally identified as a glioma-specific antigen.This study aimed to investigate the expression of Mage-d4 and its roles in tumorigenesis and cellular immune response to determine its potential as a prognosis and immunotherapeutic target for glioma.Methods:Mage-d4 expression was evaluated by immunohistochemistry(IHC) in 124 glioma specimens,among which were 84 patients followed up.To investigate the biological role of Mage-d4 in tumorigenesis,its expression was up-or down-regulated in glioma cell lines A172 and U251,followed by ts phenotypic effects were evaluated in vitro.For cellular immune response,human monocyte-derived dendritic cells(DCs) loaded with Mage-d4 recombinant protein,was used to stimulate in vitro to generate Maged4-specific cytotoxic T lymphocytes(CTLs) as demonstrated by IFN-γ production and cytotoxicity against glioma cells.Results:Mage-d4 protein was observed in 97 out of 124(78.2%) of glioma tissues tested.Furthermore,it was found to positively correlate with WHO grade and to be an independent prognostic factor for poor outcome.Down-regulation of Mage-d4 expression in U251 significantly suppressed cell growth,migration and invasion.On the contrary,these malignant behaviors were enhanced by up-regulation of Mage-d4 expression in A172.IFN-γ-producing Maged4-specific CTLs lysed Maged4-expressing HLA-A2+ U251 instead of Maged4-expressing HLA-A2-A172 in dose-dependent and HLA-A2-restricted manners.Conclusion:Our findings suggest that Mage-d4 overexpression contributes to the tumorigenesis of glioma cells and may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in glioma.
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