title: Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas.
abstract: OBJECTIVE
  To investigate the clinicopathological characteristics of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expression in the tumour microenvironments of diffuse large B cell lymphoma (DLBCL).
  
  
  RESULTS
  Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and PD-1. The expression of PD-L1 by tumour cells and/or tumour-infiltrating immune cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating PD-1(+) cells was assessed. PD-L1 expression in tumour cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B cell-like immunophenotype (16.7%) than germinal centre B cell-like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in tumour cells/macrophages showed similar clinicopathological characteristics. The quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with the level of PD-L1 expression in tumour cells (P = 0.042) or in tumour cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) cells was associated with prolonged progression-free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no prognostic significance.
  
  
  CONCLUSIONS
  PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Dohee
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Sehui
authors.initials: S
authors.lastname: Kim
authors.affiliation: Biomedical Knowledge Engineering Laboratory, Seoul National University School of Dentistry, Seoul, South Korea.
authors.forename: Pil-Jong
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
authors.affiliation: Department of Pathology, Korea Cancer Center Hospital, Seoul, South Korea.|The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.affiliation: Department of Pathology, Seoul Metropolitan Government Boramae Hospital, Seoul, South Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.|The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.|The Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.|Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: diffuse large B cell lymphoma; immunotherapy; programmed cell death 1; programmed cell death 1 ligand 1; tumour-associated macrophages