title: Natural HLA class I ligands from glioblastoma: extending the options for immunotherapy.
abstract: 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.
authors.affiliation: Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
authors.forename: Marian Christoph
authors.initials: MC
authors.lastname: Neidert
authors.forename: Oliver
authors.initials: O
authors.lastname: Schoor
authors.forename: Claudia
authors.initials: C
authors.lastname: Trautwein
authors.forename: Nico
authors.initials: N
authors.lastname: Trautwein
authors.forename: Lisa
authors.initials: L
authors.lastname: Christ
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Jürgen
authors.initials: J
authors.lastname: Honegger
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
mesh_terms: D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D000069816:SEC Translocation Channels; D053719:Tandem Mass Spectrometry
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006680:HLA Antigens; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides; D000069816:SEC Translocation Channels; C499389:SEC61G protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C516895:PTPRZ1 protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5