Genetic, tissue and circulating PD-L1 profiling to predict the response to immuno-checkpoint inhibitors in advanced NSCLC

Abstract

Abstract Background Predictive biomarkers of immune checkpoint inhibitors (ICIs) efficacy in NSCLC are still an unmet goal. PD-L1 expression at tissue level (tPD-L1) is not steadily assessable in metastatic setting and, although routinely recommended, its dynamic nature hinders an accurate estimation. Thus, the aim of our study was to determine whether embodying genetic, tissue and circulating PD-L1 status may predict ICI response in NSCLC patients. To encompass PD-L1/PD-1 axis, we investigated the incidence of PD-1 receptor on circulating T-lymphocytes. Methods Peripheral blood (PB) samples from 80 consecutive ICI-treated NSCLC patients were collected at baseline. Soluble PD-L1 (sPD-L1) was measured by Human/Cynomolgus Monkey PD-L1/B7-H1 Immunoassay (R&D Systems). PD-L1 polymorphisms (rs2282055, rs4143815) were determined by RT PCR using TaqMan® method. FACS analysis was performed to detect PD-1 expression on T cells. Available tissue sections were immunohistochemically stained for tPD-L1 scoring. All these parameters were correlated with patient characteristics, survival outcome and response to treatment. Results sPD-L1 values ranged from 14.8 to 189.8 pg/ml (median 62.8 pg/ml). High sPD-L1 and low number of PB CD8+PD-1+ lymphocytes were detected in NSCLC cases displaying ECOG PS = 2, >3 metastatic sites, liver and pleural involvement (p Conclusion Our preliminary results support sPD-L1 as a promising biomarker of ICI benefit. The simultaneous assessment of the pool size of PB PD1+ effector cells might implement the strategy to predict NSCLC survival and response to treatment. Legal entity responsible for the study University Hospital of Parma. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.