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@ARTICLE{Dejaegher:164297,
      author       = {J. Dejaegher and L. Solie and Z. Hunin and R. Sciot and D.
                      Capper$^*$ and C. Siewert$^*$ and S. Van Cauter and G. Wilms
                      and J. van Loon and N. Ectors and S. Fieuws and S.
                      Pfister$^*$ and S. W. Van Gool and S. De Vleeschouwer},
      title        = {{DNA} {M}ethylation based glioblastoma subclassification is
                      related to tumoral {T} cell infiltration and patient
                      survival.},
      journal      = {Neuro-Oncology},
      volume       = {23},
      number       = {2},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2020-02380},
      pages        = {240-250},
      year         = {2021},
      note         = {2021 Feb 25;23(2):240-250},
      abstract     = {Histologically classified Glioblastomas (GBM) can have
                      different clinical behavior and response to therapy, for
                      which molecular subclassifications have been proposed. We
                      evaluated the relationship of epigenetic GBM subgroups with
                      immune cell infiltrations, systemic immune changes during
                      radiochemotherapy and clinical outcome.450K genome-wide DNA
                      methylation was assessed on tumor tissue from 93 patients
                      with newly diagnosed GBM, treated with standard
                      radiochemotherapy and experimental immunotherapy. Tumor
                      infiltration of T cells, myeloid cells and PD-1 expression
                      were evaluated. Circulating immune cell populations and
                      selected cytokines were assessed on blood samples taken
                      before and after radiochemotherapy.Forty-two tumors had a
                      mesenchymal, 27 a RTK II, 17 a RTK I and 7 an IDH DNA
                      methylation pattern Mesenchymal tumors had the highest
                      amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH
                      tumors the lowest. There were no significant differences for
                      CD68+ cells, FoxP3+ cells and PD-1 expression between
                      groups. Systemically, there was a relative increase of CD8+
                      T cells and CD8+ PD-1 expression and a relative decrease of
                      CD4+ T cells after radiochemotherapy in all subgroups except
                      IDH tumors. Overall survival was the longest in the IDH
                      group (median 36 months), intermediate in RTK II tumors (27
                      months) and significantly lower in mesenchymal and RTK I
                      groups (15.5 and 16 months respectively).Methylation based
                      stratification of GBM is related to T cell infiltration and
                      survival, with IDH and mesenchymal tumors representing both
                      ends of a spectrum. DNA methylation profiles could be useful
                      in stratifying patients for immunotherapy trials.},
      cin          = {BE01 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33130898},
      doi          = {10.1093/neuonc/noaa247},
      url          = {https://inrepo02.dkfz.de/record/164297},
}