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Integration of spatial PD-L1 expression with the tumor immune microenvironment outperforms standard PD-L1 scoring in outcome prediction of urothelial cancer patients

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 (MIB...

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Main Authors: Weyerer, Veronika (Author) , Strissel, Pamela L. (Author) , Strick, Reiner (Author) , Sikic, Danijel (Author) , Geppert, Carol I. (Author) , Bertz, Simone (Author) , Lange, Fabienne (Author) , Taubert, Helge (Author) , Wach, Sven (Author) , Breyer, Johannes (Author) , Bolenz, Christian (Author) , Erben, Philipp (Author) , Schmitz-Draeger, Bernd J. (Author) , Wullich, Bernd (Author) , Hartmann, Arndt (Author) , Eckstein, Markus (Author)
Format: Article (Journal)
Language:English
Published: 12 May 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 10, Pages: 1-15
ISSN:2072-6694
DOI:10.3390/cancers13102327
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13102327
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/10/2327
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Author Notes:Veronika Weyerer, Pamela L. Strissel, Reiner Strick, Danijel Sikic, Carol I. Geppert, Simone Bertz, Fabienne Lange, Helge Taubert, Sven Wach, Johannes Breyer, Christian Bolenz, Philipp Erben, Bernd J. Schmitz-Draeger, Bernd Wullich, Arndt Hartmann and Markus Eckstein
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Summary: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.
Item Description:Gesehen am 16.09.2021
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers13102327

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