Tumor-Derived Extracellular Vesicles in Plasma for Predicting Anti-PD-1 Antibody Efficacy in Non-Small Cell Lung Cancer.

Liquid biopsy is a promising biomarker for cancer detection and prediction of therapy responses. In this study, we developed new antibody-based sandwich assays to measure three extracellular vesicle (EV) subsets that express cell surface vimentin (CSV) and co-express epithelial cell adhesion molecule (EpCAM) or PD-L1 in plasma. Fifty-seven non-small cell lung cancer (NSCLC) patients who underwent complete resection and 89 stage IV NSCLC patients who received anti-PD-1 antibody were enrolled. Correlations between the plasma EV subsets at baseline and various clinicopathological factors were evaluated. Plasma EpCAM/CSV-EV levels were significantly higher in stage I NSCLC patients compared to healthy donors, suggesting this may be a valuable biomarker for detecting early-stage NSCLC. High plasma CSV/CSV-EV levels at baseline were significantly correlated with a poor prognosis after treatment, both in the surgery cohort and the anti-PD-1 antibody cohort, which suggests that this may be useful for predicting the post-treatment prognosis in NSCLC patients. High plasma CSV/PD-L1-EV levels at baseline were significantly correlated with poor postoperative prognosis. However, high plasma CSV/PD-L1-EV levels at baseline were significantly correlated with a favorable clinical response and prognosis following anti-PD-1 antibody treatment in stage IV NSCLC. Therefore, plasma CSV-related EV subsets at baseline may be attractive biomarkers for early cancer detection (EpCAM/CSV), prediction of postoperative prognosis (CSV/CSV), and prediction of clinical responses and prognosis after anti-PD-1 antibody therapy (CSV/PD-L1). These EV subsets can be easily measured repetitively at appropriate timing. These novel liquid biopsies may be additional and complementary diagnostic biomarkers for NSCLC patients.