TY  - JOUR
AU  - Jurczok, Nadia
AU  - Dernbach, Gabriel
AU  - Ebner, Benedikt
AU  - Plage, Henning
AU  - Dragomir, Mihnea P
AU  - Keyl, Philipp
AU  - Ribbat-Idel, Julika
AU  - Ramberger, Evelyn
AU  - Roßner, Florian
AU  - Quaas, Alexander
AU  - Sauter, Guido
AU  - Schlomm, Thorsten
AU  - Klauschen, Frederick
AU  - Stief, Christian
AU  - Horst, David
AU  - Schulz, Gerald Bastian
AU  - Eich, Marie-Lisa
AU  - Schallenberg, Simon
TI  - Multiregional Immune Profiling Reveals Prognostic Patterns in Bladder Cancer.
JO  - European urology oncology
VL  - nn
SN  - 2588-9311
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2026-00016
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
KW  - Bladder cancer (Other)
KW  - IDO (Other)
KW  - LAG-3 (Other)
KW  - PD-1 (Other)
KW  - PD-L1 (Other)
KW  - TIM-3 (Other)
KW  - Tumor immune microenvironment (Other)
KW  - VISTA (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41475987
DO  - DOI:10.1016/j.euo.2025.12.006
UR  - https://inrepo02.dkfz.de/record/307511
ER  -