Format

Send to

Choose Destination
Acta Neuropathol. 2018 Jun;135(6):923-938. doi: 10.1007/s00401-018-1836-9. Epub 2018 Mar 20.

The natural HLA ligandome of glioblastoma stem-like cells: antigen discovery for T cell-based immunotherapy.

Author information

1
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland. marian.neidert@usz.ch.
2
Laboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland. marian.neidert@usz.ch.
3
Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
4
Laboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
5
Applied Bioinformatics, Center of Bioinformatics and Department of Computer Science, University of Tübingen, Sand 14, 72076, Tübingen, Germany.
6
DKFZ Partner Site Tübingen, German Cancer Consortium (DKTK), Auf der Morgenstelle 15, 72076, Tübingen, Germany.
7
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland.
8
Department of Hematology and Oncology, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
9
Swiss Red Cross Blood Transfusion Services Zurich and Chur, Rütistrasse 19, 8952, Zurich, Switzerland.
10
Swiss Red Cross Blood Transfusion Services Zurich and Chur, Loestrasse 170, 7000, Chur, Switzerland.
11
Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.

Abstract

Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues. Using this immunopeptidome-centric approach we could clearly delineate a subset of naturally presented, GSC-associated HLA ligands, which might serve as highly specific targets for T cell-based immunotherapy. In total, we identified 17 antigens represented by 41 different HLA ligands showing natural and exclusive presentation both on GSC and patient samples. Importantly, in vitro immunogenicity and antigen-specific target cell killing assays suggest these peptides to be epitopes of functional CD8+ T cell responses, thus rendering them prime candidates for antigen-specific immunotherapy of glioblastoma.

KEYWORDS:

GSC; Glioblastoma; Glioblastoma stem-like cells; HLA ligand; Immunotherapy; Tumor-associated antigen

PMID:
29557506
DOI:
10.1007/s00401-018-1836-9

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center