Screening for putative actionable targets reveals changes in PD-L1 expression pattern throughout biliary carcinogenesis

Intraductal papillary neoplasms (IPN) are a well-defined group of precursor lesions of biliary tract carcinoma (BTC) whose significance in the multistep model of biliary carcinogenesis is still vastly unexplored. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on both tumour and immune cells and plays an important role in promoting immune evasion. This study aimed at studying the evolution of PD L1 expression during IPN-related biliary carcinogenesis. METHODS: Intraindividually corresponding high-grade IPN (n=65), including 54 IPNB, 11 ITPN and their associated invasive BTC (n=46) were selected for TMA construction. Immunohistochemistry and chromogen-in-situ-hybridization were employed to assess the expression of various targetable biomarkers, including p16, p53, c-myc, c-met, EGFR, HER2, BRAF and PD-L1. These results were correlated with our previously studied spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis focusing on infiltrating immune cell populations. RESULTS: In 6.2% BTC patients including only distal cholangiocarcinoma, IPN cells expressed PD-L1 at a Tumor Proportion Score (TPS) cut-off of 1%. Higher PD-L1 levels above 1% and 10% Combined Positive Score (CPS) also considering PD-L1 expressing immune cells were reached in 7.7% and 50.8% of BTC cases, respectively. At a 1% cut-off, TPS was associated with distinct histomorphological IPN-subtypes and UICC-Stages. PD-L1 expression in IPN was associated with increased total, stromal and intraepithelial CD3+-, CD4+- and CD8+-immune cell densities. In contrast, only a significant correlation between PD L1 expression and CD8+-cell density was found in the corresponding BTC tissue. We here showed that PD-L1 expression undergoes dynamic changes throughout IPN-driven carcinogenesis.

Publication History

Article published online:
23 January 2024