% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Scheck:307510,
      author       = {J. Scheck$^*$ and B. Boztepe$^*$ and J. M. Kernbach and K.
                      Karimian-Jazi and L. Heinz and K. Schregel and V. Sturm and
                      M. Schell and J. Bojcevski$^*$ and M. Fischer and R. Eurich
                      and I. Poschke$^*$ and J. Schwarz and D. A. Agardy$^*$ and
                      S. Jünger$^*$ and C. Schulz and F. Althammer and A. R.
                      Osidach and A. Abdollahi$^*$ and L. Bunse$^*$ and V.
                      Venkataramani$^*$ and S. M. Pfister$^*$ and F. Winkler$^*$
                      and T. Kessler$^*$ and W. Wick$^*$ and S. Heiland and M.
                      Platten$^*$ and C. Rodell and M. Bendszus and I.
                      Weidenfeld$^*$ and M. Breckwoldt$^*$},
      title        = {{M}ultimodality mapping of immunotherapy distribution as a
                      predictive marker in glioma.},
      journal      = {Neuro-Oncology},
      volume       = {nn},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2026-00015},
      pages        = {nn},
      year         = {2025},
      note         = {#EA:E210#LA:E210#LA:D170# / epub},
      abstract     = {Scarce T cell infiltration, immunosuppressive
                      tumor-associated macrophages and ineffective drug delivery
                      drive glioma progression and limit treatment efficacy.
                      Mapping immunotherapy distribution by multimodality imaging
                      might be a biomarker that could aid tumor monitoring and
                      guide therapy development.To assess drug delivery, we
                      developed a MRI-lightsheet microscopy platform (MR-LSM) to
                      monitor immunotherapy at the cellular level in two
                      immunocompetent glioma models (Gl261, SB28). The
                      atezolizumab (PD-L1 inhibitor) subgroup of the multicenter
                      N2M2/NOA20 trial in MGMT unmethylated GBM patients was
                      assessed by CNN analysis and correlated to progression free
                      survival.In contrast to the conventional Gl261 glioma model,
                      SB28 gliomas are characterized by poor immunogenicity and
                      resistance to Toll-like receptor (TLR) 7 targeted therapy
                      delivered by CDNP-R848 nanoparticles. SB28 resistance is
                      driven by microvascular pathology, vasogenic edema and drug
                      off-targeting to peritumoral edema and white matter tracts.
                      Vascular endothelial growth factor (VEGF) inhibition in
                      conjunction with irradiation and dual immunotherapy (DIR)
                      targeting innate (CDNP-R848) and adaptive immunity
                      (anti-CTLA-4) breaks resistance, increases survival and
                      reverses drug off-targeting. Mechanistically, tumor control
                      is orchestrated by vascular normalization, enhanced CD8+ T
                      cell influx and a proinflammatory shift of myeloid cells
                      along with strong IL-12/IL-13 upregulation. In a
                      translational analysis of the multicenter N2M2/NOA20 trial
                      we validate that edema and microvascular pathology are
                      associated with poor prognosis in glioblastoma patients
                      treated with checkpoint immunotherapy and that patients
                      without edema have increased PFS.We develop a customizable
                      imaging platform to map drug delivery to glioma with broad
                      applicability in neuroscience and neurooncology.},
      keywords     = {blood-brain barrier disruption (Other) / drug distribution
                      (Other) / glioma (Other) / immunotherapy (Other) / tumor
                      microenvironment (Other)},
      cin          = {E210 / D170 / HD01 / B062 / B320},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)D170-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B320-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41476211},
      doi          = {10.1093/neuonc/noaf295},
      url          = {https://inrepo02.dkfz.de/record/307510},
}