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  • 1
    Publication Date: 2018-06-16
    Description: Purpose: Successful immunotherapies for IDH mut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design: Protein fractionations of tissue lysates from IDH mut gliomas ( n = 4) were performed. Fractions were tested by IFN ELISpot assay for recognition through patients' T cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico -predicted synthetic long peptides in patients of origin, additional IDH mut glioma patients ( n = 16), and healthy donors ( n = 13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDH mut glioma stem-like cells (GSC). HLA-A*02–restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T cells by HLA-peptide tetramer analysis. Results: A total of 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process, 79 proteins were selected as potential T-cell antigens. Twenty-six of these were recognized by the patients’ T cells, and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDH mut glioma patients. Most immunogenic tumor-associated antigens (TAA) were expressed in IDH mut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02–restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T cells in IDH mut glioma patients. Conclusions: By analyzing the repertoire of T-cell target antigens in IDH mut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDH mut tumors and GSCs. Clin Cancer Res; 24(12); 2951–62. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Journal/Serial
    Journal/Serial
    Oxford [u.a.] : Taylor & Francis | Oxford : BIOS Publ. Ltd. | Abingdon [u.a.] : BIOS Scientific Publ.
    Print: 54.2002 – 58.2006 (Location: QH301Z:36)
    Continued as: SEB experimental biology series  (2008–)
    Publisher: Oxford [u.a.] : Taylor & Francis , Oxford : BIOS Publ. Ltd. , Abingdon [u.a.] : BIOS Scientific Publ.
    Corporation: Society for Experimental Biology
    Topics: Biology
    Parallel titles: Symposium Series
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  • 3
    Journal/Serial
    Journal/Serial
    Cambridge : Univ. Press
    Print: 1.1947 – 53.2001 (Location: QH301Z:36)
    Continued as: SEB symposium series  (2002–2007)
    Publisher: Cambridge : Univ. Press
    Corporation: Society for Experimental Biology
    Print ISSN: 0081-1386
    Topics: Biology
    Abbreviation: Symp. Soc. Exp. Biol.
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  • 4
    Journal cover
    Journal/Serial
    Sevenoaks : Arnold | London [u.a.] : Sage Publ. | Sage Publications (früher: Hodder Arnold) | HighWire Press
    partly licensed Journals Online: 1.1992 – (Not the last 2 years) (Go to Journal)
    Print: 2.1993 – 16.2007 (Location: W1Z:117)
    Publisher: Sevenoaks : Arnold , London [u.a.] : Sage Publ. , Sage Publications (früher: Hodder Arnold) , HighWire Press
    Print ISSN: 0962-2802
    Electronic ISSN: 1477-0334
    Topics: Medicine
    Keywords: Biometrie ; Statistik ; Medizin
    Parallel titles: SM in MR
    Abbreviation: Stat Methods Med Res
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  • 5
    Journal cover
    Journal/Serial
    München : Urban & Vogel | Urban & Vogel bei Springer LINK | Heidelberg : Springer Medizin | Heidelberg : Springer | München : Springer Medizin, Urban & Vogel
    Print: 162.1986 – 185.2009 (Location: WN1Z:2)
    licenced Journals Online: 173.1997 – (Go to Journal)
    Formerly as: Strahlentherapie  (1912–1985)
    Supplement: Informationen  (1980–1997)
    Supplement: Medizin-Forum aktuell  (1996–2011)
    Supplement: Cancer care  (1994–2007)
    Publisher: München : Urban & Vogel , Urban & Vogel bei Springer LINK , Heidelberg : Springer Medizin , Heidelberg : Springer , München : Springer Medizin, Urban & Vogel
    Print ISSN: 0179-7158
    Electronic ISSN: 1439-099X
    Topics: Medicine
    Keywords: Radiologie ; Zeitschrift ; Lähmung ; Onkologie ; Krebs ; Jahrbuch ; Strahlenbiologie ; Medizinische Radiologie ; Strahlentherapie
    Parallel titles: Industrie-Information , Strahlentherapie und Onkologie / Supplement
    Abbreviation: Strahlenther Onkol
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  • 6
    Journal/Serial
    Journal/Serial
    Wien | Berlin : Urban & Schwarzenberg | München | München : Urban & Schwarzenberg
    Print: 1.1912 – 161.1985 (Location: WN1Z:2)
    Continued as: Strahlentherapie und Onkologie  (1986–)
    Supplement: DRG-Informationen  (1972–1979)
    Supplement: Informationen  (1980–1997)
    Publisher: Wien , Berlin : Urban & Schwarzenberg , München , München : Urban & Schwarzenberg
    Print ISSN: 0039-2073
    Topics: Medicine
    Keywords: Zeitschrift ; Strahlentherapie
    Abbreviation: Strahlentherapie
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  • 7
    Online Resource
    Online Resource
    Science Journal Publication
    free Journals Online: 2011 – (Go to Journal)
    Publisher: Science Journal Publication
    Electronic ISSN: 2276-6324
    Topics: Mathematics
    Keywords: Allgemeine Mathematik ; Mathematische Statistik
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  • 8
    Online Resource
    Online Resource
    Secrétariat Mathématique, Paris | Faculté des Sciences de Paris | NUMDAM
    free Journals Online: 1.1957 – 7.1967 (Go to Journal)
    Publisher: Secrétariat Mathématique, Paris , Faculté des Sciences de Paris , NUMDAM
    Topics: Mathematics
    Keywords: Seminarberichte ; Analysis
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  • 9
    Online Resource
    Online Resource
    Sports Medicine Australia
    free Journals Online: 22(1)2004 – (Go to Journal)
    Publisher: Sports Medicine Australia
    Print ISSN: 1032-5662 , 0812-8308
    Topics: Sports Science , Medicine
    Keywords: Sportmedizin
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  • 10
    Online Resource
    Online Resource
    Sage Publications
    partly licensed Journals Online: 1.2009 – (Not the last 2 years) (Go to Journal)
    Publisher: Sage Publications
    Print ISSN: 1941-7381
    Electronic ISSN: 1941-0921
    Topics: Sports Science , Medicine
    Keywords: Sportmedizin
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