Programmed cell death ligand-1 (PD-L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti-PD-L1 antibodies.

ABSTRACT

AIMS: Pembrolizumab has shown promising results for patients with programmed cell death ligand-1 (PD-L1)-positive advanced biliary tract cancer in an ongoing clinical trial. However, data on PD-L1 expression in bile duct cancers is limited, and the frequency of PD-L1 positivity varies, which may be partly due to the assay used. The aim of this study was to evaluate PD-L1 expression status in bile duct cancers by using 22C3, SP263 and E1L3N antibodies. METHODS AND RESULTS: We evaluated PD-L1 expression in tissue microarrays of 183 extrahepatic bile duct cancers, including 89 perihilar and 94 distal bile duct cancers, by using 22C3, SP263 and E1L3N. When the 22C3 assay was used, tumoral PD-L1 was shown to be expressed in 16.9% of cases at a 1% threshold. When the SP263 and E1L3N assays were used, tumoral PD-L1 was shown to be expressed in 26% and 7.1% of cases, respectively. When whole tissue sections were examined, 59.6% of PD-L1-positive cases showed a low percentage (<10%) of positive tumour cells. Tumoral PD-L1 positivity was associated with poor histological differentiation (P = 0.017) and the biliary epithelial phenotype (P = 0.041). High tumoral PD-L1 expression (≥10%) was associated with worse overall survival (OS) and disease-free survival (DFS) (OS, P = 0.012; DFS, P = 0.042). CONCLUSIONS: PD-L1 was expressed in a small subset of patients with bile duct cancer, and the percentage of positive tumour cells was low in PD-L1-positive cases. The SP263 assay showed the highest PD-L1 positivity in both tumour cells and immune cells, followed by the 22C3 and E1L3N assays. High PD-L1 expression was associated with a poor prognosis in extrahepatic bile duct cancer patients.