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Quantifying PD1 saturation by PDL1 in tumor tissue using a novel RNA aptamer-based assay.
Biorxiv : the Preprint Server for Biology
|April 17, 2026
Summary
A new assay, PD1 Ligand Receptor Complex Aptamer (LIRECAP), quantifies PD1 saturation by PDL1 in tumors. This biomarker can predict patient response to anti-PD1 therapy, improving treatment selection.
Area of Science:
- Biomarker Discovery
- Molecular Diagnostics
- Cancer Immunotherapy
Background:
- Predicting patient response to PD1/PDL1 therapies remains a challenge.
- Novel predictive biomarkers are crucial for optimizing anti-PD1 treatment efficacy.
- Quantifying PD1 saturation by PDL1 in tumor tissue offers potential as a predictive biomarker.
Purpose of the Study:
- To develop and validate a novel bioassay for quantifying PD1 saturation by PDL1.
- To assess the utility of this assay as a predictive biomarker for anti-PD1 therapy.
Main Methods:
- Development of the PD1 Ligand Receptor Complex Aptamer (LIRECAP) assay using RNA aptamers.
- Quantification of PD1 saturation via a 2-color qRT-PCR measuring the ratio of C to P aptamers.
- Validation in formalin-fixed paraffin-embedded (FFPE) sarcoma biospecimens.
Main Results:
- The LIRECAP assay accurately quantifies PD1 saturation by PDL1 in FFPE tumor samples.
- Assay results correlated with PD1-mediated signaling and PD1-PDL1 proximity.
- Significant inter-patient variability and intratumoral heterogeneity in PD1 saturation were observed.
Conclusions:
- The PD1 LIRECAP assay is a novel, feasible, and reproducible method for quantifying PD1 saturation by PDL1.
- This assay holds potential as a superior predictive biomarker for PD1/PDL1-based immunotherapy.
- The platform may be adaptable for quantifying other molecular interactions.
