Weyerer, Veronika and Strissel, Pamela L. and Strick, Reiner and Sikic, Danijel and Geppert, Carol I. and Bertz, Simone and Lange, Fabienne and Taubert, Helge and Wach, Sven and Breyer, Johannes and Bolenz, Christian and Erben, Philipp and Schmitz-Draeger, Bernd J. and Wullich, Bernd and Hartmann, Arndt and Eckstein, Markus (2021) Integration of Spatial PD-L1 Expression with the Tumor Immune Microenvironment Outperforms Standard PD-L1 Scoring in Outcome Prediction of Urothelial Cancer Patients. CANCERS, 13 (10): 2327. ISSN , 2072-6694
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Simple Summary Diagnostic PD-L1 assessment of urothelial cancer to predict a patient's immune therapy response remains a matter of controversy. Several contributing factors have been discussed; however, systematic studies are lacking. The present study demonstrates that clinically applied PD-L1 scoring algorithms are influenced by inter-algorithm variability and result in the selection of different "PD-L1" positive populations within the tumor immune microenvironment (TIME). The results further demonstrate that specific immune phenotypes of muscle-invasive urothelial cancer are associated with very different clinical outcomes, which cannot be resolved by PD-L1 testing. Thus, PD-L1 alone not only fails to reflect the TIME, but also has implications for patients. We conclude that a comprehensive integration of PD-L1 expression and immune phenotypes is superior to PD-L1 testing. This might be a novel strategy to predict a patient's response to immune therapy. 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 Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEATH LIGAND-1; INFILTRATING LYMPHOCYTES; BLADDER-CANCER; SQUAMOUS-CELL; OPEN-LABEL; CARCINOMA; ATEZOLIZUMAB; MULTICENTER; IMMUNOTHERAPY; CHEMOTHERAPY; bladder cancer; urothelial cancer; immune phenotypes; PD-L1; PD-1; TILs |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 06:42 |
| Last Modified: | 21 Sep 2022 06:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47774 |
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