Assessment of PD-L1 expression in circulating tumor cells in patients with breast cancer.

Abstract

e13001 Background: Evidence is accumulating that the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced breast cancer patients. PD-L1 tumor expression is emerging as a potential biomarker in PD-1/PD-L1 checkpoint blockade therapies. However, PD-L1 expression on tumor tissue is limited by the temporal and spatial heterogeneity as well as insufficient tumor tissue samples. PD-L1 expression in circulating tumor cells (CTCs) might overcome the limitation. We investigated the utility of CTCs as a noninvasive method to evaluate PD-L1 status in breast cancer patients. Methods: 46 breast cancer patients including 42 metastatic breast cancer patients and four early breast cancer patients were enrolled. CTCs were collected from peripheral blood samples using a microfluidic-based CTC separator. A novel staining procedure which included fluorescent glucose analog staining and immunostaining targeting CD45, vimentin and PD-L1 were analyzed. PD-L1 expression level was analyzed as the fraction of PD-L1 positive CTCs among total CTCs. Results: 46 breast cancer patients all had detected CTCs, ranging from 12 to 110. The fraction of PD-L1 positive CTCs varied from 2.08% to 85.69%. PD-L1 expression was obviously higher in triple negative breast cancer (TNBC) patients as compared with non-TNBC patients (47.16% vs 26.23%, P < 0.01). Interestingly, we observed that PD-L1 positive CTCs were also detected in four early TNBC patients. No significant association was found between PD-L1 expression and mesenchymal CTC phenotype. Conclusions: These data suggest that assessment of PD-L1 expression in CTCs from breast cancer patients is feasible. PD-L1 expression in CTCs might serve as a complementary tool for PD-L1 expression analysis in breast cancer patients.