Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small cell lung cancer

Abstract

Background

Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small cell lung cancer (NSCLC) and emerged as potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a non-invasive method to evaluate PD-L1 status in advanced NSCLC patients.

Patients and Methods

CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform, Rarecells) from 106 NSCLC patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody, Ventana), and quantified in tumor cells and WBCs.

Results

CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4ml, and median of 60 CTCs/4ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥ 1 PD-L1 positive CTCs, and 11 patients (15%) showed ≥ 1% PD-L1 positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (Sensitivity=55%; Specificity=100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥ 1% PD-L1 positive immune infiltrates in tumor tissue, and 39 patients (53%) showed ≥ 1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (Sensitivity=82%; Specificity=79%).We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in circulating tumor or immune cells (PFS and OS), similar to the effects of PD-L1 expression in matched-patient tumors.

Conclusions

These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a non-invasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.