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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

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PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision

Elisa Baldelli¹, K Alex Hodge¹, Guido Bellezza²

¹Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USA.

Journal for Immunotherapy of Cancer

|October 8, 2021

Summary

This summary is machine-generated.

This study found that different antibody clones for programmed cell death ligand 1 (PD-L1) show varied performance in cancer testing. High-throughput assays can identify tumors with low PD-L1 expression that may not respond to treatment.

Keywords:

B7-H1 antigen biomarkers lung neoplasms tumor

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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Published on: September 25, 2018

Area of Science:

Oncology
Immunotherapy
Biomarker Discovery

Background:

Anti-programmed cell death protein 1 (PD-1) and PD-L1 agents are key cancer treatments.
Immunohistochemistry assays for PD-L1 expression have limitations, including variable predictive value and lack of standardized cut-offs.
This variability hinders optimal patient selection for immunotherapy.

Purpose of the Study:

To compare the performance of six anti-PD-L1 antibody clones using a high-throughput immunoassay.
To assess the concordance between different antibody clones in measuring PD-L1 expression across various tumor types.
To evaluate the utility of RPPA-based PD-L1 measurements in predicting response to nivolumab treatment.

Main Methods:

Utilized reverse phase protein microarray (RPPA) with fluorescence detection to analyze PD-L1 expression.
Tested six anti-PD-L1 antibody clones (22C3, 28-8, CAL10, E1L3N, SP142, and atezolizumab) on 666 tumor samples from lung, ovarian, prostate, and breast cancers.
Included diverse sample types (frozen, FFPE, biopsies) and isolated pure tumor epithelia via laser capture microdissection.

Main Results:

Significant heterogeneity in PD-L1 expression levels (0.01-39.37) and concordance (correlation coefficients -0.48 to 0.95) was observed among the six antibody clones.
Correlation coefficients below 0.50 were found in 61% of clone comparisons, indicating poor agreement.
RPPA measurements in nivolumab-treated lung cancer patients identified a subgroup with low PD-L1 expression that did not respond to treatment.

Conclusions:

Continuous RPPA measurements provide a broad dynamic range for PD-L1 expression and reveal heterogeneous antibody clone concordance.
This high-throughput immunoassay approach shows potential for identifying specific tumor subgroups that may not benefit from PD-L1 targeted therapies.
RPPA offers a promising tool for refining PD-L1 biomarker assessment in clinical practice.