PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma

// Jacqueline Fontugne 1, 2, 3 , Jeremy Augustin 1 , Anais Pujals 1, 3 , Philippe Compagnon 3, 4 , Benoit Rousseau 2, 3, 5 , Alain Luciani 2, 3, 6 , Christophe Tournigand 3, 5 , Daniel Cherqui 7 , Daniel Azoulay 3, 4 , Jean-Michel Pawlotsky 2, 3, 8 , Julien Calderaro 1, 2, 3 1 AP-HP, Groupe Hospitalier Henri Mondor, Departement de Pathologie, Creteil, France 2 INSERM, U955, Team 18, Institut Mondor de Recherche Biomedicale, Creteil, France 3 Universite Paris Est Creteil, Creteil, France 4 AP-HP, Groupe Hospitalier Henri Mondor, Departement de Chirurgie Hepato-Biliaire et Transplantation Hepatique, Creteil, France 5 AP-HP, Groupe Hospitalier Henri Mondor, Departement d’Oncologie Medicale, Creteil, France 6 AP-HP, Groupe Hospitalier Henri Mondor, Departement d’Imagerie Medicale, Creteil, France 7 AP-HP, Centre Hepatobiliaire, Service de Chirurgie Hepatobiliaire, Hopital Paul Brousse, Creteil, France 8 AP-HP, Groupe Hospitalier Henri Mondor, Service de Virologie, Bacteriologie-Hygiene, Mycologie-Parasitologie et Unite Transversale de Traitement des Infections, Creteil, France Correspondence to: Jacqueline Fontugne, email: fontugnej@gmail.com Keywords: cholangiocarcinoma, PD-1, PD-L1, immunotherapy Received: August 02, 2016      Accepted: February 12, 2017      Published: February 21, 2017 ABSTRACT Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression. A series of 58 iCCAs and 41 pCCAs was included in the study. PD-L1, PD-1 and CD3 expression was investigated using immunohistochemistry. Density of TILs was evaluated by immunohistochemistry using a quantitative score of CD3-stained intratumoral lymphocytes. PD-L1 expression by neoplastic cells was observed in 9 cases (9%, 5 iCCAs and 4 pCCAs). PD-L1 positive inflammatory cell aggregates were identified in 46% ( n = 46) of the cases (31 iCCAs and 15 pCCAs). PD-L1 expression by either neoplastic or inflammatory cells was associated to high density of CD3-positive TILs ( p = 0.01 and p = 0.005, respectively). The number of PD-L1 positive inflammatory cell aggregates was higher in tumors with high PD-1 expression ( p < 0.0001). Altogether, PD-L1 in iCCA and pCCA is mainly expressed in tumors with high density of TILs. Our results suggest that CCAs with dense intratumoral lymphocytic infiltration might represent good candidates for PD-L1/PD-1 blocking agents.