Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy

• Published in: Journal of neuro-oncology 2013-02, Vol.111 (3), p.285-294
• Main Authors: Neidert, Marian Christoph, Schoor, Oliver, Trautwein, Claudia, Trautwein, Nico, Christ, Lisa, Melms, Arthur, Honegger, Jürgen, Rammensee, Hans-Georg, Herold-Mende, Christel, Dietrich, Pierre-Yves, Stevanović, Stefan
• Format: Article
• Language: English
• Subjects: Antigen (tumor-associated); Brain Neoplasms - classification; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; DNA microarrays; Epidermal growth factor receptors; Gene expression; Gene Expression Regulation, Neoplastic - physiology; Glial Fibrillary Acidic Protein - metabolism; Glioblastoma; Glioblastoma - classification; Glioblastoma - metabolism; Glioblastoma - pathology; glioblastoma multiforme; Glioma; Histocompatibility antigen HLA; HLA Antigens - metabolism; Humans; Immunotherapy; Laboratory Investigation; Ligands; Medicine; Medicine & Public Health; Membrane Proteins - metabolism; Neurology; Oligonucleotides; Oncology; Peptides - metabolism; Prognosis; Receptor, Epidermal Growth Factor - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - metabolism; SEC Translocation Channels; Tandem Mass Spectrometry
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-012-1028-8

Glioblastoma multiforme is the most frequent and most malignant primary brain tumor with poor prognosis despite surgical removal and radio-chemotherapy. In this setting, immunotherapeutical strategies have great potential, but the reported repertoire of tumor associated antigens is only for HLA-A*02 positive tumors. We describe the first analysis of HLA-peptide presentation patterns in HLA-A*02 negative glioma tissue combined with gene expression profiling of the tumor samples by oligonucleotide microarrays. We identified numerous candidate peptides for immunotherapy. These are peptides derived from proteins with a well-described role in glioma tumor biology and suitable gene expression profiles such as PTPRZ1, EGFR, SEC61G and TNC. Information obtained from complementary analyses of HLA-A*02 negative tumors not only contributes to the discovery of novel shared glioma antigens, but most importantly provides the opportunity to tailor a patient-individual cocktail of tumor-associated peptides for a personalized, targeted immunotherapeutic approach in HLA-A*02 negative patients.