Integration of spatial PD-L1 expression with the tumor immune microenvironment outperforms standard PD-L1 scoring in outcome prediction of urothelial cancer patients
dc.contributor.author | Weyerer, Veronika | |
dc.contributor.author | Strissel, Pamela L. | |
dc.contributor.author | Strick, Reiner | |
dc.contributor.author | Sikic, Danijel | |
dc.contributor.author | Geppert, Carol I. | |
dc.contributor.author | Bertz, Simone | |
dc.contributor.author | Lange, Fabienne | |
dc.contributor.author | Taubert, Helge | |
dc.contributor.author | Wach, Sven | |
dc.contributor.author | Breyer, Johannes | |
dc.contributor.author | Bolenz, Christian | |
dc.contributor.author | Erben, Philipp | |
dc.contributor.author | Schmitz-Draeger, Bernd J. | |
dc.contributor.author | Wullich, Bernd | |
dc.contributor.author | Hartmann, Arndt | |
dc.contributor.author | Eckstein, Markus | |
dc.date.accessioned | 2021-05-20T14:46:59Z | |
dc.date.available | 2021-05-20T14:46:59Z | |
dc.date.issued | 2021-05-02 | |
dc.identifier.uri | http://hdl.handle.net/10713/15718 | |
dc.description.abstract | Background: Immune therapy has gained significant importance in managing urothelial cancer. The value of PD-L1 remains a matter of controversy, thus requiring an in-depth analysis of its biological and clinical relevance. Methods: A total of 193 tumors of muscle-invasive bladder cancer patients (MIBC) were assessed with four PD-L1 assays. PD-L1 scoring results were correlated with data from a comprehensive digital-spatial immune-profiling panel using descriptive statistics, hierarchical clustering and uni-/multivariable survival analyses. Results: PD-L1 scoring algorithms are heterogeneous (agreements from 63.1% to 87.7%), and stems from different constellations of immune and tumor cells (IC/TC). While Ventana IC5% algorithm identifies tumors with high inflammation and favorable baseline prognosis, CPS10 and the TCarea25%/ICarea25% algorithm identify tumors with TC and IC expression. Spatially organized immune phenotypes, which correlate either with high PD-L1 IC expression and favorable prognosis or constitutive PD-L1 TC expression and poor baseline prognosis, cannot be resolved properly by PD-L1 algorithms. PD-L1 negative tumors with relevant immune infiltration can be detected by sTILs scoring on HE slides and digital CD8+ scoring. Conclusions: Contemporary PD-L1 scoring algorithms are not sufficient to resolve spatially distributed MIBC immune phenotypes and their clinical implications. A more comprehensive view of immune phenotypes along with the integration of spatial PD-L1 expression on IC and TC is necessary in order to stratify patients for ICI. © 2021 by the authors. | en_US |
dc.description.sponsorship | Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg | en_US |
dc.description.uri | https://doi.org/10.3390/cancers13102327 | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI AG | en_US |
dc.relation.ispartof | Cancers | en_US |
dc.subject | Bladder cancer | en_US |
dc.subject | Immune phenotypes | en_US |
dc.subject | PD-1 | en_US |
dc.subject | PD-L1 | en_US |
dc.subject | TILs | en_US |
dc.subject | Urothelial cancer | en_US |
dc.title | Integration of spatial PD-L1 expression with the tumor immune microenvironment outperforms standard PD-L1 scoring in outcome prediction of urothelial cancer patients | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.3390/cancers13102327 | |
dc.source.volume | 13 | |
dc.source.issue | 10 |