MAGED4 – expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue

Abstract

MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

“…MAGED4 mRNA was also reportedly upregulated 2.6 to 15 folds in glioblastoma, relatively to cultured human astrocytes ). Then, another study (Kramer et al, 2005) got the similar result for MAGED4 mRNA expression. A MHC class I ligand from MAGED4 presented by HLA-A on tumor tissue was also identified in this report (Kramer et al, 2005).…”

“…Then, another study (Kramer et al, 2005) got the similar result for MAGED4 mRNA expression. A MHC class I ligand from MAGED4 presented by HLA-A on tumor tissue was also identified in this report (Kramer et al, 2005). Recent studies have shown that MAGED4 contributes to proliferation, migration, and invasion of tumor cells in breast cancer and oral squamous cell carcinoma (Germano et al, 2011;Chong et al, 2012).…”

“…Studies evaluating the MAGED4 expression in normal tissues and glioma are limited Kramer et al, 2005). This study demonstrated by use of conventional RT-PCR that normal tissues express MAGED4 mRNA in more than half samples tested.…”

“…It was reported that MAGED4 is overexpressed in many human malignancies, including glioma, kidney cancer, lung cancer, breast cancer and oral squamous carcinoma Kramer et al, 2005;Ito et al, 2006;Germano et al, 2011;Chong et al, 2012). Although all of glioblastomas tested by previous reports Kramer et al, 2005) is positive for the MAGED4 mRNA, the number tested is too limited and lack of information for protein expression.…”

“…Through qRT-PCR, MAGED4 demonstrated a very low level of expression in normal tissues with MAGED4 mRNA. Kramer et al (2005) have examined a panel of normal tissues and comfirmed that most normal tissues did not express MAGED4 mRNA, even if some normal tissues expressed MAGED4 mRNA, compared to glioma, they also showed low MAGED4 expression. In our study, many tissue types were different with previous reports Kramer et al, 2005).…”