Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy.
In this study, we investigated the mRNA and protein expression of nine tumour antigens in human glioblastoma multiforme with a view to their possible use in dendritic cell-based immunotherapy. Expression of ALK, EGFRvIII, GALT3, gp100, IL-13Ralpha2, MAGE-A3, NA17-A, TRP-2 and tyrosinase were studied by real-time RT-PCR on frozen tissues using a series of 47 tumour samples from patients with glioblastoma. Results were compared with non-neoplastic brain expression or glioblastoma samples with very low levels of expression near the limits of detection for EGFRvIII and MAGE-A3, as these latter two antigens were not detected in non-neoplastic brain. Tumour antigens showing a 5-fold increase in mRNA expression were considered as positive, and only antigens displaying an mRNA over-expression in a significant number of cases were analysed by immunohistochemistry on paraffin-embedded sections. Using real time RT-PCR, we found EGFRvIII, gp100, IL-13Ralpha2 and TRP-2 to be positive in 64, 38, 32 and 21% of cases, respectively. While we observed no over-expression for ALK, GALT3 and tyrosinase, 3 samples out of 47 were positive for MAGE-3 and 1 sample for NA17-A. More than 25% of tumour cells showed strong protein expression in 13, 34, 85 and 96% of GBM samples for gp100, TRP-2, EGFRvIII and IL-13Ralpha2, respectively. Interestingly, protein expression of at least 3 antigens was observed in 38% of cases. These results point out the importance of EGFRvIII, IL-13Ralpha2 and, to a less extent gp100 and TRP-2, for developing an immunotherapy strategy against glioblastoma.
Saikali
Stéphan
S
Département d'Anatomie et cytologie pathologiques, Hôpital Pontchaillou, Rennes, France.
Avril
Tony
T
Collet
Brigitte
B
Hamlat
Abderrahmane
A
Bansard
Jean-Yves
JY
Drenou
Bernard
B
Guegan
Yvon
Y
Quillien
Véronique
V
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053663:Interleukin-13 Receptor alpha2 Subunit; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C548637:PMEL protein, human; D012333:RNA, Messenger; C113139:Trp2 protein, vertebrate; C410723:epidermal growth factor receptor VIII; D058951:gp100 Melanoma Antigen; D066246:ErbB Receptors