title: PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes.
abstract: Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes.
  
  
  
  We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylin-eosin-safran-stained slides.
  
  
  
  PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles, ATS scores were maximal at 8 in 100%, 100%, and 75% of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity.
  
  
  
  We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti-PD-L1 drug in GTD patients has been activated.
authors.affiliation: *Department of Gynecological Surgery and Oncology, Obstetrics, and †French Center for Trophoblastic Diseases, University Hospitals of Lyon; and ‡Joint Unit Hospices Civils de Lyon-bioMerieux, University Hospital Lyon Sud, Pierre Bénite; §Department of Pathology, University Hospital of Rouen, Rouen; ∥University Hospital Femme Mere Enfant, Department of Prenatal Diagnosis; and ¶Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Bron; and #Department of Pathology, University Hospital La Croix Rousse; **Department of Medical Oncology, HCL Cancer Institute, University Hospitals of Lyon; and ††Lyon 1 University, Lyon, France.
authors.forename: Pierre-Adrien
authors.initials: PA
authors.lastname: Bolze
authors.forename: Sophie
authors.initials: S
authors.lastname: Patrier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Massardier
authors.forename: Touria
authors.initials: T
authors.lastname: Hajri
authors.forename: Fatima
authors.initials: F
authors.lastname: Abbas
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Schott
authors.forename: Fabienne
authors.initials: F
authors.lastname: Allias
authors.forename: Mojgan
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.forename: Gilles
authors.initials: G
authors.lastname: Freyer
authors.forename: François
authors.initials: F
authors.lastname: Golfier
authors.forename: Benoît
authors.initials: B
authors.lastname: You
mesh_terms: D000328:Adult; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D011379:Prognosis; D014327:Trophoblasts / Q000276:immunology* / Q000473:pathology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human