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Cited by 201Immunotherapy and Immune Responsesvaccines and immunoinformatics approachesGlioma Diagnosis and Treatment

Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy

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Dutoit, Valérie, Herold-Mende, Christel, Hilf, Norbert, Schoor, Oliver, Beckhove, Philipp, Bucher, Judith, Dorsch, Katharina, Flohr, Sylvia +12 more·2012·Brain
DOI 10.1093/brain/aws042
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Abstract

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.

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Crossref · 10.1093/brain/aws042

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  • The NLGN4X epitope encoded by CVGBM is over-presented on GBM tumours compared with healthy brain tissue.

    “NLGN4X is less over-expressed in GBM; however, the encoded epitope is over-presented on GBM tumours compared with healthy brain tissue [28].”

    From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [28]

    The Selection and characterization section identifies NLGN4X 131–139 among the selected peptides and reports that all ten were either detected only on tumour cells or over-presented on GBM compared with normal tissues, including normal brain. Our copy does not identify CVGBM as encoding the epitope, so it does not support that part of the claim. Page numbers were not provided for these passages. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The epitopes are derived from four TAAs that are either over-expressed (BCAN, BIRC5, PTPRZ1) or over-presented (NLGNX4) in a large proportion of GBM tumours compared with most healthy tissues.

    “The epitopes are derived from four TAAs that are either over-expressed (BCAN, BIRC5, PTPRZ1 [Supplementary Fig. 1b]) or where the epitope is over-presented (NLGNX4) in a large proportion of GBM tumours compared with most healthy tissues [28].”

    From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [28]

    The Selection and characterization section reports higher antigen expression and peptide presentation in GBM than in healthy tissues, and Table 1 identifies peptides derived from BCAN, PTPRZ1 and NLGN4X. It does not list a BIRC5-derived peptide, so it does not support that part of the four-antigen claim. The source spells the fourth antigen NLGN4X, rather than NLGNX4. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 4

  1. Chekenya M, Hjelstuen M, Enger PO, Thorsen F, Jacob AL, Probst B, et al. NG2 proteoglycan promotes angiogenesis-dependent tumor growth in CNS by sequestering angiostatin. FASEB J 2002; 16: 586-8.
  2. Dunn GP, Dunn IF, Curry WT. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun 2007; 7: 12-27.
  3. Schirle M, Keilholz W, Weber B, Gouttefangeas C, Dumrese T, Becker HD, et al. Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach. Eur J Immunol 2000; 30: 2216-25.
  4. Sehgal A, Boynton AL, Young RF, Vermeulen SS, Yonemura KS, Kohler EP, et al. Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. Int J Cancer 1998; 76: 451-8.

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Authors
Dutoit, V., Herold-Mende, C., Hilf, N., Schoor, O., Beckhove, P., Bucher, J., Dorsch, K., Flohr, S., Fritsche, J., Lewandrowski, P., Lohr, J., Rammensee, H.-G., Stevanovic, S., Trautwein, C., Vass, V., Walter, S., Walker, P. R., Weinschenk, T., Singh-Jasuja, H., & Dietrich, P.-Y.
Affiliations
  • University Hospital of Geneva (CH)
  • Immatics Biotechnologies (Germany) (DE)
  • German Cancer Research Center (DE)
  • Heidelberg University (DE)
  • University of Tübingen (DE)
  • University of Geneva (CH)
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2012-02-14
Volume
135
Issue
4
Pages
1042-1054
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/aws042
OpenAlex
W2078461037
Cited by
201
References
39
Citations by year
2026: 6 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 7 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 23 · 2017: 23 · 2016: 14 · 2015: 21 · 2014: 11 · 2013: 14 · 2012: 6
FWCI
7.24
Type
journal article
Language
en
Open access
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • reroDoc Digital Library (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Bundesministerium für Bildung und Forschung (0315253, 0315120A)
  • Ligue Contre le Cancer
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Keywords
glioblastoma, tumor-associated antigens, HLA-A*02, HLA-bound peptides, CD8+ T cells, cancer immunotherapy, tumor-specific T cells, T cell tolerance, multipeptide vaccine, gliomagenesis
MeSH terms
Antigens, Neoplasm, Brain Neoplasms, Chromatography, Liquid, Flow Cytometry, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Peptides, RNA, Messenger, Mass Spectrometry, HLA-A Antigens, Antigens, CD, Cytokines, Antigen Presentation, CD8-Positive T-Lymphocytes, Platelet Endothelial Cell Adhesion Molecule-1, Oligonucleotide Array Sequence Analysis, Sequence Analysis, Protein, Gene Expression Profiling, Receptor-Like Protein Tyrosine Phosphatases, Class 5

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