Functional binding of PD1 ligands predicts response to anti-PD1 treatment in patients with cancer

Bar Kaufman, Orli Abramov, Anna Ievko, Daria Apple, Mark Shlapobersky, Irit Allon, Yariv Greenshpan, Baisali Bhattachrya, Ofir Cohen, Tatiana Charkovsky, Alexandra Gayster, Ruthy Shaco-Levy, Keren Rouvinov, Alejandro Livoff, Moshe Elkabets, Angel Porgador

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Accurate predictive biomarkers of response to immune checkpoint inhibitors (ICIs) are required for better stratifying patients with cancer to ICI treatments. Here, we present a new concept for a bioassay to predict the response to anti-PD1 therapies, which is based on measuring the binding functionality of PDL1 and PDL2 to their receptor, PD1. In detail, we developed a cell-based reporting system, called the immuno-checkpoint artificial reporter with overexpression of PD1 (IcAR-PD1) and evaluated the functionality of PDL1 and PDL2 binding in tumor cell lines, patient-derived xenografts, and fixed-tissue tumor samples obtained from patients with cancer. In a retrospective clinical study, we found that the functionality of PDL1 and PDL2 predicts response to anti-PD1 and that the functionality of PDL1 binding is a more effective predictor than PDL1 protein expression alone. Our findings suggest that assessing the functionality of ligand binding is superior to staining of protein expression for predicting response to ICIs.

Original languageEnglish
Article numbereadg2809
Pages (from-to)eadg2809
JournalScience advances
Volume9
Issue number21
DOIs
StatePublished - 26 May 2023

ASJC Scopus subject areas

  • General

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