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dc.contributor.authorWeyerer, Veronika
dc.contributor.authorStrissel, Pamela L.
dc.contributor.authorStrick, Reiner
dc.contributor.authorSikic, Danijel
dc.contributor.authorGeppert, Carol I.
dc.contributor.authorBertz, Simone
dc.contributor.authorLange, Fabienne
dc.contributor.authorTaubert, Helge
dc.contributor.authorWach, Sven
dc.contributor.authorBreyer, Johannes
dc.contributor.authorBolenz, Christian
dc.contributor.authorErben, Philipp
dc.contributor.authorSchmitz-Draeger, Bernd J.
dc.contributor.authorWullich, Bernd
dc.contributor.authorHartmann, Arndt
dc.contributor.authorEckstein, Markus
dc.date.accessioned2021-05-20T14:46:59Z
dc.date.available2021-05-20T14:46:59Z
dc.date.issued2021-05-02
dc.identifier.urihttp://hdl.handle.net/10713/15718
dc.description.abstractBackground: 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.sponsorshipInterdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburgen_US
dc.description.urihttps://doi.org/10.3390/cancers13102327en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancersen_US
dc.subjectBladder canceren_US
dc.subjectImmune phenotypesen_US
dc.subjectPD-1en_US
dc.subjectPD-L1en_US
dc.subjectTILsen_US
dc.subjectUrothelial canceren_US
dc.titleIntegration of spatial PD-L1 expression with the tumor immune microenvironment outperforms standard PD-L1 scoring in outcome prediction of urothelial cancer patientsen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers13102327
dc.source.volume13
dc.source.issue10


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