TY  - JOUR
AU  - Marcu, Ana
AU  - Schlosser, Andreas
AU  - Keupp, Anne
AU  - Trautwein, Nico
AU  - Johann, Pascal
AU  - Wölfl, Matthias
AU  - Lager, Johanna
AU  - Monoranu, Camelia Maria
AU  - Walz, Juliane S
AU  - Henkel, Lisa M
AU  - Krauß, Jürgen
AU  - Ebinger, Martin
AU  - Schuhmann, Martin
AU  - Thomale, Ulrich Wilhelm
AU  - Pietsch, Torsten
AU  - Klinker, Erdwine
AU  - Schlegel, Paul G
AU  - Oyen, Florian
AU  - Reisner, Yair
AU  - Rammensee, Hans-Georg
AU  - Eyrich, Matthias
TI  - Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors.
JO  - Journal for ImmunoTherapy of Cancer
VL  - 9
IS  - 10
SN  - 2051-1426
CY  - London
PB  - BioMed Central
M1  - DKFZ-2021-02090
SP  - e003404 
PY  - 2021
AB  - Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS tumors of infancy and early childhood. Hallmark is the surprisingly simple genome with inactivating mutations or deletions in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T cells. However, it is unclear which epitopes T cells might recognize on AT/RT cells.Here, we report a comprehensive mass spectrometry (MS)-based analysis of naturally presented human leukocyte antigen (HLA) class I and class II ligands on 23 AT/RTs. MS data were validated by matching with a human proteome dataset and exclusion of peptides that are part of the human benignome. Cryptic peptide ligands were identified using Peptide-PRISM.Comparative HLA ligandome analysis of the HLA ligandome revealed 55 class I and 139 class II tumor-exclusive peptides. No peptide originated from the SMARCB1 region. In addition, 61 HLA class I tumor-exclusive peptide sequences derived from non-canonically translated proteins. Combination of peptides from natural and cryptic class I and class II origin gave optimal representation of tumor cell compartments. Substantial overlap existed with the cryptic immunopeptidome of glioblastomas, but no concordance was found with extracranial tumors. More than 80
KW  - antigens (Other)
KW  - epitope mapping (Other)
KW  - immunotherapy (Other)
KW  - neoplasm (Other)
KW  - pediatrics (Other)
KW  - vaccination (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34599019
DO  - DOI:10.1136/jitc-2021-003404
UR  - https://inrepo02.dkfz.de/record/172542
ER  -