BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG) antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. OBJECTIVE: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. METHODS: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. RESULTS: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHC class II expression. CONCLUSIONS: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell-mediated immunotherapy in neuroblastoma.
BACKGROUND:Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG) antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. OBJECTIVE: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. METHODS: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. RESULTS: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHC class II expression. CONCLUSIONS: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell-mediated immunotherapy in neuroblastoma.
Authors: Chrystal U Louis; Barbara Savoldo; Gianpietro Dotti; Martin Pule; Eric Yvon; G Doug Myers; Claudia Rossig; Heidi V Russell; Oumar Diouf; Enli Liu; Hao Liu; Meng-Fen Wu; Adrian P Gee; Zhuyong Mei; Cliona M Rooney; Helen E Heslop; Malcolm K Brenner Journal: Blood Date: 2011-10-07 Impact factor: 22.113
Authors: Kellie B Haworth; Jennifer L Leddon; Chun-Yu Chen; Edwin M Horwitz; Crystal L Mackall; Timothy P Cripe Journal: Pediatr Blood Cancer Date: 2014-12-18 Impact factor: 3.167
Authors: Elena Grau; Silvestre Oltra; Francisco Martínez; Carmen Orellana; Adela Cañete; Jose María Fernández; Miguel Hernández-Martí; Victoria Castel Journal: J Cancer Res Clin Oncol Date: 2008-09-27 Impact factor: 4.553
Authors: Michael A Sheard; Shahab Asgharzadeh; Yin Liu; Tsen-Yin Lin; Hong-Wei Wu; Lingyun Ji; Susan Groshen; Dean A Lee; Robert C Seeger Journal: J Immunother Date: 2013-06 Impact factor: 4.456
Authors: Gregor S D Reid; Xiaochuan Shan; Christina M Coughlin; Wiem Lassoued; Bruce R Pawel; Leonard H Wexler; Carol J Thiele; Maria Tsokos; Jack L Pinkus; Geraldine S Pinkus; Stephan A Grupp; Robert H Vonderheide Journal: Clin Cancer Res Date: 2009-10-13 Impact factor: 12.531