The natural HLA ligandome of glioblastoma stem-like cells: antigen discovery for T cell-based immunotherapy
| Autor: | Marian Christoph Neidert, Patrick Roth, Luca Regli, Konstantina Kapolou, Janet Kerstin Peper, Manfred Westphal, Stefan Stevanovic, Ana Marcu, Fabian Wolpert, Günter Eisele, Daniel J. Kowalewski, Michael Weller, Reinhard Henschler, Sophie S. Wang, Hans-Georg Rammensee, Lena Katharina Freudenmann, Juliane S. Walz, Manuela Silginer, Katrin Lamszus, Linus Backert |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_treatment T cell Human leukocyte antigen Biology CD8-Positive T-Lymphocytes Ligands Epitope Pathology and Forensic Medicine Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Antigen HLA Antigens Cell Line Tumor medicine Humans Child Aged Aged 80 and over Brain Neoplasms Immunogenicity Brain Immunotherapy Middle Aged Isocitrate Dehydrogenase 030104 developmental biology Cell killing medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Female Neurology (clinical) Glioblastoma CD8 |
| Zdroj: | Acta neuropathologica. 135(6) |
| ISSN: | 1432-0533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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