Abstract A118: Clinical impact of PD-L1 expression and epithelial-mesenchymal transition in the tumor microenvironment of extrahepatic cholangiocarcinoma

Background: Extrahepatic cholangiocarcinoma (eCCA) has a poor prognosis. Although the possibility of immunotherapy has been studied, immune checkpoint molecules such as programmed death ligand 1 (PD-L1) in eCCA are not well understood. Epithelial-mesenchymal transition (EMT) has recently been shown to regulate PD-L1 expression. Our aims were to assess the clinicopathological significance of tumor-infiltrating lymphocytes (TILs) and tumor PD-L1 expression in eCCA and to compare these immune responses with EMT marker expression. Material and Methods: An immunohistochemical evaluation using a TMA method at a single large center was performed. Patients (n = 117) underwent surgical resection in the Department of Gastroenterological Surgery II at Hokkaido University Hospital between January 1995 and November 2006 and eCCA tumors were confirmed histopathologically. We investigated the level of infiltration of immune cells positive for CD4, CD8, Foxp3, PD-L1 in addition to E-cadherin, N-cadherin, Vimentin, ZEB1, ZEB2, SNAIL, TWIST expression, statistically comparing correlations among these factors. Results: High numbers of CD4+ and CD8+ TILs correlated with node-negative (P = 0.009 and P = 0.046, respectively) and low SNAIL expression (P = 0.016 and P = 0.022, respectively). High PD-L1 expression was associated with poor histopathologic classification (P = 0.034), and low E-cadherin (P = 0.001), high N-cadherin (P = 0.044), high vimentin (P < 0.001) and high ZEB1 (P = 0.036) expression. Multivariate analysis showed that CD4+ TILs, PD-L1 expression and N-cadherin expression were independent prognostic factors (hazard ratio (HR) = 0.61; 95% confidence interval (CI) = 0.38-1.00; HR=4.27; 95% CI = 1.82-9.39; HR = 2.20; 95% CI = 1.18-3.92, respectively). Summary: Present data suggested that CD4+ T lymphocyte tumor infiltration and PD-L1 expression on tumor cells were independent prognostic factors in eCCA. We also provided the first evidence that high tumor PD-L1 expression correlates with a mesenchymal phenotype. Citation Format: Takahiro Tsuchikawa, Takashi Ueno, Osamu Sato, Toru Nakamura, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Keisuke Okamura, Toshiaki Shichinohe, Satoshi Hirano. Clinical impact of PD-L1 expression and epithelial-mesenchymal transition in the tumor microenvironment of extrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A118.