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@ARTICLE{Jurczok:307511,
      author       = {N. Jurczok and G. Dernbach and B. Ebner and H. Plage and M.
                      P. Dragomir$^*$ and P. Keyl and J. Ribbat-Idel and E.
                      Ramberger and F. Roßner and A. Quaas and G. Sauter and T.
                      Schlomm and F. Klauschen$^*$ and C. Stief and D. Horst and
                      G. B. Schulz and M.-L. Eich and S. Schallenberg},
      title        = {{M}ultiregional {I}mmune {P}rofiling {R}eveals {P}rognostic
                      {P}atterns in {B}ladder {C}ancer.},
      journal      = {European urology oncology},
      volume       = {nn},
      issn         = {2588-9311},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2026-00016},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Muscle-invasive bladder cancer (MIBC) is a biologically
                      heterogeneous disease with variable prognosis after radical
                      cystectomy. While conventional clinicopathological
                      parameters offer limited prognostic value, growing evidence
                      highlights the role of the tumor immune microenvironment
                      (TIME)-including immune cell composition and spatial
                      architecture-as robust biomarkers for disease progression
                      and outcomes.The study included 251 consecutive patients
                      with MIBC who underwent cystectomy (2004-2014, LMU Munich).
                      Three 1-mm-diameter cores were sampled from the tumor
                      invasive front and center in the cystectomy specimen. Six
                      immune checkpoint proteins (ICPs; IDO, PD-L1, PD-1, LAG-3,
                      TIM-3, and VISTA) were quantified digitally following
                      immunohistochemical (IHC) staining. ICP-positive immune and
                      tumor cells were stratified and densities were
                      hierarchically clustered. Multivariable Cox models were then
                      used to assess the association with overall (OS) and
                      disease-free survival. The minimum tumor sample count needed
                      to detect the maximum ICP expression per patient was
                      estimated via a 1000-fold bootstrap resampling
                      simulation.IDO+ and VISTA+ immune cells dominated the TIME,
                      while PD-L1+ tumor cells exhibited a dichotomous expression
                      pattern. Analysis of three spatially distinct cores was
                      sufficient to recover maximal expression of low-abundance
                      TIM-3+ and VISTA+ immune cells, while four cores were
                      required for all other markers. ICP-based clustering
                      revealed three TIME subtypes (CID1-3), of which CID3 was
                      associated with markedly worse prognosis (median OS 18.5 vs
                      100.5 mo; p = 0.0007). This classification outperformed
                      Union for International Cancer Control staging and improved
                      patient stratification in late-stage MIBC.A six-marker,
                      multiregional ICP panel delivers a robust,
                      stage-independent, actionable risk stratification in MIBC.
                      At least four biopsies are advised for routine immune
                      profiling; further longitudinal external validation is
                      warranted.},
      keywords     = {Bladder cancer (Other) / IDO (Other) / LAG-3 (Other) / PD-1
                      (Other) / PD-L1 (Other) / TIM-3 (Other) / Tumor immune
                      microenvironment (Other) / VISTA (Other)},
      cin          = {BE01 / MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41475987},
      doi          = {10.1016/j.euo.2025.12.006},
      url          = {https://inrepo02.dkfz.de/record/307511},
}