Exosomal PD-L1 expression as non-invasive biomarker for immune checkpoint inhibitors in non-small cell lung cancer

Abstract

Abstract The development of immune checkpoint inhibitors (ICIs) significantly improved survival outcomes of non-small cell lung cancer (NSCLC) patients compared to chemotherapy. However, identification of predictive exosomal biomarker to reduce the invasive biopsy as well as to understand the efficacy of ICIs in NSCLC patients are unexplored. In this investigation, we demonstrate for the first time exosomal PD-L1 expression as predictive biomarker (liquid biopsy) for immune checkpoint blockage with PD-1/PD-L1 inhibitors in advanced/metastatic NSCLC. Plasma samples from NSCLC patients (n=25) with matched paired samples at baseline and after 8 weeks of PD-1 blockade (Nivolumab, pembrolizumab and atezolizumab) were utilized for exosomal PD-L1 analysis by immunoblot. No statistically significant differences were reported for PD-L1 changes between pretreatment samples and at 8 weeks in both progressive patients (p=0.3783) and non-progressing patients (p=0.8066). Interestingly, when considering PD-L1 changes at 8 weeks between patients with progressive disease and partial response/stable disease (non-progressors), a trend towards PD-L1 reduction was observed in the non-progressors group, albeit this difference was not statistically significant (p=0.1941) due to the small sample size. Interestingly, dynamic changes during treatment of exosomal PD-L1 expression, assessed as exosomal PD-L1 ratio between pretreated samples and after 8 weeks of treatment, predicted the outcome of ICI treated patients in terms of both PFS and OS. In conclusion, reduced exosomal PD-L1 expression at 8 weeks observed in non-progressors suggesting that exosomal PD-L1 might be used as non-invasive serum marker for ICIs treatment in NSCLC patients.