Title : PD-1/PD-L1 interaction is a predictive biomarker to stratify NSCLC lung cancer patients to immunotherapy
Abstract:
Non–small cell lung carcinoma (NSCLC) is known to evade host immune defenses via a downregulation of the immune response. One of the molecules involved in this mechanism is programmed cell death ligand 1 (PD-L1), which interacts with its receptor, programmed cell death protein 1 (PD-1), expressed on T-cells, leading to a reduction in cytokine release and cytotoxic activity, as well as a halt in T-cell proliferation. Approved therapeutic monoclonal antibodies which target PD-1/PD-L1 interactions are revolutionizing cancer treatments, however a significant subset of patients does not benefit from these expensive treatments. PD-L1 expression determined by immunohistochemistry (IHC) on tumor tissue is the clinically validated predictive biomarker. Nevertheless, only evaluating PD-L1 expression cannot accurately ensure correct patient selection for treatment, due to survival benefits being observed in anti-PD-1/PD-L1 treated patients regardless of their PD-L1 expression.
To address this issue we have developed QF-Pro, a novel antibody-based imaging assay utilizing amplified Förster resonance energy transfer (FRET) for the quantification of PD-1/PD-L1 interactions in NSCLC tissue samples (FFPE). The analysis across a cohort of 135 patients demonstrated the intra- and inter-tumoral heterogeneity of the interacting PD-1/PD-L1 immune checkpoint and notably showed the correlation between PD?1/PD?L1 interaction levels and patients’ overall survival (OS).
