Research Papers:
PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma
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Abstract
Jacqueline Fontugne1,2,3, Jérémy Augustin1, Anaïs Pujals1,3, Philippe Compagnon3,4, Benoit Rousseau2,3,5, Alain Luciani2,3,6, Christophe Tournigand3,5, Daniel Cherqui7, Daniel Azoulay3,4, Jean-Michel Pawlotsky2,3,8, Julien Calderaro1,2,3
1AP-HP, Groupe Hospitalier Henri Mondor, Département de Pathologie, Créteil, France
2INSERM, U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France
3Université Paris Est Créteil, Créteil, France
4AP-HP, Groupe Hospitalier Henri Mondor, Département de Chirurgie Hépato-Biliaire et Transplantation Hépatique, Créteil, France
5AP-HP, Groupe Hospitalier Henri Mondor, Département d’Oncologie Médicale, Créteil, France
6AP-HP, Groupe Hospitalier Henri Mondor, Département d’Imagerie Médicale, Créteil, France
7AP-HP, Centre Hépatobiliaire, Service de Chirurgie Hépatobiliaire, Hopital Paul Brousse, Créteil, France
8AP-HP, Groupe Hospitalier Henri Mondor, Service de Virologie, Bactériologie-Hygiène, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Créteil, France
Correspondence to:
Jacqueline Fontugne, email: [email protected]
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.
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PII: 15602