Integration of spatial pd-l1 expression with the tumor immune microenvironment outperforms standard pd-l1 scoring in outcome prediction of urothelial cancer patients

Weyerer V, Strissel P, Strick R, Sikic D, Geppert CI, Bertz S, Lange F, Taubert H, Wach S, Breyer J, Bolenz C, Erben P, Schmitz-Draeger BJ, Wullich B, Hartmann A, Eckstein M (2021)

Publication Type: Journal article, Original article

Publication year: 2021

Journal

Cancers MDPI

Book Volume: 13

Article Number: 2327

Journal Issue: 10

DOI: 10.3390/cancers13102327

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.

Authors with CRIS profile

Veronika Bahlinger Institute of Pathology Pamela Strissel Medizinische Fakultät Reiner Strick Medizinische Fakultät Danijel Sikic Medizinische Fakultät Carol-Immanuel Geppert Institute of Pathology Simone Bertz Institute of Pathology Fabienne Lange Institute of Pathology Helge Taubert Professur für Molekulare Urologie Sven Wach Medizinische Fakultät Bernd Wullich Lehrstuhl für Urologie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Markus Eckstein Institute of Pathology

Involved external institutions

BRIDGE Consortium e.V. (Bladder Cancer Research Initiative for Drug Targets Germany) DE Germany (DE)

How to cite

APA:

Weyerer, V., Strissel, P., Strick, R., Sikic, D., Geppert, C.-I., Bertz, S.,... Eckstein, M. (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). https://doi.org/10.3390/cancers13102327

MLA:

Weyerer, Veronika, et al. "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 (2021).

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