title: Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features.
abstract: The prognosis of hepatocellular carcinoma (HCC) remains poor, with only one third of patients eligible for curative treatments and very limited survival benefits with the use of sorafenib, the current standard of care for advanced disease. Recently, agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) immune checkpoint were shown to display impressive antitumor activity in various solid or hematological malignancies, including HCC. PD-L1 immunohistochemical expression is thought to represent a biomarker predictive of drug sensitivity. Here, we investigated PD-L1 expression in a series of 217 HCCs and correlated our results with clinical and histological features and immunohistochemical markers (PD-1, cytokeratin 19, glutamine synthetase, and β-catenin expression). PD-L1 expression by neoplastic cells was significantly associated with common markers of tumor aggressiveness (high serum alpha-fetoprotein levels, P = 0.038; satellite nodules, P < 0.001; macrovascular invasion, P < 0.001; microvascular invasion, P < 0.001; poor differentiation, P < 0.001) and with the progenitor subtype of HCC (cytokeratin 19 expression, P = 0.031). High PD-L1 expression by inflammatory cells from the tumor microenvironment also correlated with high serum alpha-fetoprotein levels (P < 0.001), macrovascular invasion (P = 0.001), poor differentiation (P = 0.001), high PD-1 expression (P < 0.001), and the so-called lymphoepithelioma-like histological subtype of HCC (P = 0.003).
  
  
  
  PD-L1 expression by either neoplastic or intratumoral inflammatory cells is related to tumor aggressiveness and suggests that the response to treatments targeting the PD-L1/PD-1 immune checkpoint could be restricted to particular HCC variants; thus, enrichment of these tumor subtypes in future clinical trials should be considered. (Hepatology 2016;64:2038-2046).
authors.affiliation: Département de Pathologie, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.|INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Calderaro
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.|Service d'Oncologie Médicale, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.|Service d'Hépatologie, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Amaddeo
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Mercey
authors.affiliation: Département de Pathologie, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Charpy
authors.affiliation: Service d'Hépatologie, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Costentin
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.|Service d'Imagerie Médicale, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Luciani
authors.affiliation: Département de Pathologie, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Elie-Serge
authors.initials: ES
authors.lastname: Zafrani
authors.affiliation: Service de Chirurgie Digestive et Hépatobiliaire, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Laurent
authors.affiliation: Université Paris-Est Créteil, Créteil, France.|Service de Chirurgie Digestive et Hépatobiliaire, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.
authors.forename: Fouad
authors.initials: F
authors.lastname: Lafdil
authors.affiliation: INSERM U955, Team 18, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris-Est Créteil, Créteil, France.|Service de Virologie, Bactériologie-Hygiène, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human