%0 Journal Article
%A Jurczok, Nadia
%A Dernbach, Gabriel
%A Ebner, Benedikt
%A Plage, Henning
%A Dragomir, Mihnea P
%A Keyl, Philipp
%A Ribbat-Idel, Julika
%A Ramberger, Evelyn
%A Roßner, Florian
%A Quaas, Alexander
%A Sauter, Guido
%A Schlomm, Thorsten
%A Klauschen, Frederick
%A Stief, Christian
%A Horst, David
%A Schulz, Gerald Bastian
%A Eich, Marie-Lisa
%A Schallenberg, Simon
%T Multiregional Immune Profiling Reveals Prognostic Patterns in Bladder Cancer.
%J European urology oncology
%V nn
%@ 2588-9311
%C Amsterdam
%I Elsevier
%M DKFZ-2026-00016
%P nn
%D 2025
%Z epub
%X 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.
%K Bladder cancer (Other)
%K IDO (Other)
%K LAG-3 (Other)
%K PD-1 (Other)
%K PD-L1 (Other)
%K TIM-3 (Other)
%K Tumor immune microenvironment (Other)
%K VISTA (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41475987
%R 10.1016/j.euo.2025.12.006
%U https://inrepo02.dkfz.de/record/307511