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There and back again: PD-L1 Positivity as a Biomarker for Immune Checkpoint Blockade in Urothelial Carcinoma
Arivarasan Karunamurthy1, Diwakar Davar1,2
1University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, Pennsylvania.
Abstract:
Biomarkers of responsiveness to immune checkpoint blockade (ICB) are heavily sought given the breadth and depth of the use of ICB in cancer. PD-L1 expression was among the first biomarkers identified, but multiple factors have precluded more widespread use. In this issue, Galsky and colleagues utilize two separate PD-L1 assays to study urothelial carcinoma specimens and observe that SP142 (relative to 22C3) preferentially stains dendritic cells. These observations may help reconcile the discordant performance of the two PD-L1 assays in ICB-treated urothelial carcinoma while underscoring the role of dendritic cells in orchestrating ICB response. See related article by Galsky et al., p. 476 .
Insights
Researchers investigated immune checkpoint blockade (ICB) biomarkers in urothelial carcinoma. They found that the SP142 assay, unlike 22C3, highlights dendritic cells, potentially explaining differing ICB response predictions.
Area of Science:
- Immunooncology
- Cancer Biomarkers
- Urothelial Carcinoma Research
Background:
- Immune checkpoint blockade (ICB) is a crucial cancer therapy, necessitating reliable biomarkers for treatment response.
- Programmed death-ligand 1 (PD-L1) expression is an established biomarker, but its clinical utility is limited by assay variability.
- Understanding PD-L1 staining differences is vital for optimizing ICB efficacy in urothelial carcinoma.
Purpose of the Study:
- To compare the staining patterns of two distinct PD-L1 assays (SP142 and 22C3) in urothelial carcinoma specimens.
- To investigate the differential cellular expression of PD-L1 by these assays.
- To explore how these differences may impact the prediction of response to immune checkpoint blockade.
Main Methods:
- Analysis of urothelial carcinoma tissue specimens.
- Utilized two commercially available PD-L1 immunohistochemistry assays: SP142 and 22C3.
- Comparative assessment of staining intensity and cellular localization between the two assays.
Main Results:
- The SP142 assay demonstrated preferential staining of dendritic cells compared to the 22C3 assay.
- Observed distinct cellular targets for PD-L1 expression between the SP142 and 22C3 assays.
- These differential staining patterns may explain discordant results from PD-L1 assays in predicting ICB response.
Conclusions:
- The SP142 and 22C3 PD-L1 assays exhibit differential cellular tropism, particularly in staining dendritic cells.
- Dendritic cells play a significant role in orchestrating the response to immune checkpoint blockade.
- These findings provide a potential explanation for discrepancies in PD-L1 biomarker performance and guide future biomarker development for ICB therapy.
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