Functional binding of PD1 ligands predicts response to anti-PD1 treatment in patients with cancer
Menée à l'aide de lignées cellulaires, d'une xénogreffe sur un modèle murin et d'échantillons tumoraux prélevés sur des patients atteints d'un cancer, cette étude met en évidence une association entre l'activité de liaison de PDL1/2 et la réponse aux anti-PD1
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. Positive clinical response of cancer patients to anti-PD1 therapy can be predicted by measuring the binding activity of PDL1/2.
Science Advances , article en libre accès, 2022