Integration of Spatial PD-L1 Expression with the Tumor Immune Microenvironment Outperforms Standard PD-L1 Scoring in Outcome Prediction of Urothelial Cancer Patients

摘要

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.