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@ARTICLE{Marcu:172542,
      author       = {A. Marcu and A. Schlosser and A. Keupp and N. Trautwein and
                      P. Johann$^*$ and M. Wölfl and J. Lager and C. M. Monoranu
                      and J. S. Walz$^*$ and L. M. Henkel and J. Krauß and M.
                      Ebinger and M. Schuhmann and U. W. Thomale and T. Pietsch
                      and E. Klinker and P. G. Schlegel and F. Oyen and Y. Reisner
                      and H.-G. Rammensee and M. Eyrich},
      title        = {{N}atural and cryptic peptides dominate the immunopeptidome
                      of atypical teratoid rhabdoid tumors.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {9},
      number       = {10},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2021-02090},
      pages        = {e003404},
      year         = {2021},
      abstract     = {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
                      $80\%$ of AT/RT exclusive peptides were able to successfully
                      prime CD8+ T cells, whereas naturally occurring memory
                      responses in AT/RT patients could only be detected for class
                      II epitopes. Interestingly, $>50\%$ of AT/RT exclusive class
                      II ligands were also recognized by T cells from glioblastoma
                      patients but not from healthy donors.These findings
                      highlight that AT/RTs, potentially paradigmatic for other
                      pediatric tumors with a low mutational load, present a
                      variety of highly immunogenic HLA class I and class II
                      peptides from canonical as well as non-canonical protein
                      sources. Inclusion of such cryptic peptides into therapeutic
                      vaccines would enable an optimized mapping of the tumor cell
                      surface, thereby reducing the likelihood of immune evasion.},
      keywords     = {antigens (Other) / epitope mapping (Other) / immunotherapy
                      (Other) / neoplasm (Other) / pediatrics (Other) /
                      vaccination (Other)},
      cin          = {B062 / TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)TU01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34599019},
      doi          = {10.1136/jitc-2021-003404},
      url          = {https://inrepo02.dkfz.de/record/172542},
}