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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Bibliographic Details
Published in:Cancers 2021-05, Vol.13 (10), p.2327
Main Authors: Weyerer, Veronika, Strissel, Pamela L., Strick, Reiner, Sikic, Danijel, Geppert, Carol I., Bertz, Simone, Lange, Fabienne, Taubert, Helge, Wach, Sven, Breyer, Johannes, Bolenz, Christian, Erben, Philipp, Schmitz-Draeger, Bernd J., Wullich, Bernd, Hartmann, Arndt, Eckstein, Markus
Format: Article
Language:English
Subjects:
Algorithms
Apoptosis
Bladder cancer
Cancer therapies
CD8 antigen
Chemotherapy
Immunology
Immunotherapy
Inflammation
Integration
Invasiveness
Ligands
Lymphocytes
Medical prognosis
Metastases
Microenvironments
Patients
PD-L1 protein
Phenotypes
Prognosis
Proteins
Statistical analysis
Tumor cells
Tumors
Urothelial cancer
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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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13102327