The natural HLA ligandome of glioblastoma stem-like cells
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The natural HLA ligandome of glioblastoma stem-like cells : antigen discovery for T cell-based immunotherapy. / Neidert, Marian Christoph; Kowalewski, Daniel Johannes; Silginer, Manuela; Kapolou, Konstantina; Backert, Linus; Freudenmann, Lena Katharina; Peper, Janet Kerstin; Marcu, Ana; Wang, Sophie Shih-Yüng; Walz, Juliane Sarah; Wolpert, Fabian; Rammensee, Hans-Georg; Henschler, Reinhard; Lamszus, Katrin; Westphal, Manfred; Roth, Patrick; Regli, Luca; Stevanović, Stefan; Weller, Michael; Eisele, Günter.
In: ACTA NEUROPATHOL, Vol. 135, No. 6, 06.2018, p. 923-938.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The natural HLA ligandome of glioblastoma stem-like cells
T2 - antigen discovery for T cell-based immunotherapy
AU - Neidert, Marian Christoph
AU - Kowalewski, Daniel Johannes
AU - Silginer, Manuela
AU - Kapolou, Konstantina
AU - Backert, Linus
AU - Freudenmann, Lena Katharina
AU - Peper, Janet Kerstin
AU - Marcu, Ana
AU - Wang, Sophie Shih-Yüng
AU - Walz, Juliane Sarah
AU - Wolpert, Fabian
AU - Rammensee, Hans-Georg
AU - Henschler, Reinhard
AU - Lamszus, Katrin
AU - Westphal, Manfred
AU - Roth, Patrick
AU - Regli, Luca
AU - Stevanović, Stefan
AU - Weller, Michael
AU - Eisele, Günter
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
U2 - 10.1007/s00401-018-1836-9
DO - 10.1007/s00401-018-1836-9
M3 - SCORING: Journal article
C2 - 29557506
VL - 135
SP - 923
EP - 938
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -