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

J Neurooncol. 2013 Feb;111(3):285-94. doi: 10.1007/s11060-012-1028-8. Epub 2012 Dec 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / classification
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioblastoma / classification
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • HLA Antigens / metabolism*
  • Humans
  • Ligands
  • Membrane Proteins / metabolism
  • Peptides / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • SEC Translocation Channels
  • Tandem Mass Spectrometry

Substances

  • Glial Fibrillary Acidic Protein
  • HLA Antigens
  • Ligands
  • Membrane Proteins
  • Peptides
  • SEC Translocation Channels
  • SEC61G protein, human
  • EGFR protein, human
  • ErbB Receptors
  • PTPRZ1 protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5