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@ARTICLE{Monnikhof:303120,
      author       = {M. Monnikhof and M. Y. Schakelaar and C. Meulenbroeks and
                      M. Quist and A. Perzolli and A. Selten and C. J. M. Koster
                      and D. S. C. Maassen and A. Montoro Canelo and M. Fredriks
                      and M. J. A. Koppers and K. Clevers and J. Klein and V.
                      Kaludjerovic and J. Meeldijk and E. W. Pijnappel and H. G.
                      Rebel and S. van Kempen and S. Crnko and T. Koorman and A.
                      Federico and F. Valzano and P. Wesseling and F. G. J.
                      Calkoen and J. van der Lugt and T. Ten Broeke and M.
                      Kool$^*$ and N. Bovenschen},
      title        = {{D}ual targeting of {CD}155/{TIGIT} and {PD}-{L}1/{PD}-1
                      immune checkpoints potentiates {NK} cell-mediated
                      cytotoxicity in medulloblastoma.},
      journal      = {Neuro-oncology advances},
      volume       = {7},
      number       = {1},
      issn         = {2632-2498},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2025-01539},
      pages        = {vdaf099},
      year         = {2025},
      abstract     = {Medulloblastoma (MB) is one of the most prevalent pediatric
                      brain malignancies and makes up approximately $20\%$ of all
                      primary brain tumors in children. Current treatment options
                      are not curative for approximately $30\%$ of patients and
                      leave survivors with an impaired quality of life. Immune
                      checkpoint inhibition can offer a novel targeted therapy but
                      largely remains understudied in MB. The aim of this study
                      was to determine whether dual immune checkpoint inhibition
                      can be used as a novel targeted therapy in MB.We utilized
                      single cell and single nuclei sequencing datasets of primary
                      MB tumors, established Group 3 and Sonic Hedgehog MB cell
                      lines and MB patient-derived xenograft (PDX) organoid
                      models, and primary patient-derived MB tissue of all
                      subtypes to study immune checkpoints and their blockade to
                      target MB.We identified the expression of immune checkpoint
                      protein CD155 on MB tumor cells and the expression of its
                      inhibitory binding partner TIGIT on immune cells of MB
                      patient-derived tissues, cell lines, and PDX MB organoids.
                      In addition, while MB shows weak, if any, PD-L1 protein
                      expression, we found that MB cells can upregulate PD-L1
                      expression upon stimulation by natural killer (NK) cells or
                      interferon-γ as a putative immune evasive strategy.
                      Subsequent immunotherapeutic interventions with FDA-approved
                      antibodies Tiragolumab (anti-TIGIT), Durvalumab (anti-PD-1),
                      and their combination potentiated primary NK cell activation
                      and killing of MB cell lines and PDX-derived MB
                      organoids.These data propose a translatable and novel
                      immunotherapeutic strategy for children diagnosed with
                      subgroups Sonic Hedgehog and Group 3 MB.},
      keywords     = {CD155/TIGIT (Other) / PD-L1/PD-1 (Other) / immune
                      checkpoints (Other) / medulloblastoma (Other) / organoids
                      (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40703802},
      pmc          = {pmc:PMC12284645},
      doi          = {10.1093/noajnl/vdaf099},
      url          = {https://inrepo02.dkfz.de/record/303120},
}