title: Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma.
abstract: Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1(+) DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1(+) DLBCL. We also defined the criteria for microenvironmental PD-L1(+) (mPD-L1(+)) DLBCL (ie, PD-L1(-) DLBCL in which PD-L1(+) nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1(+) tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1(+) and mPD-L1(+) DLBCL were 11% and 15.3%, respectively. Both PD-L1(+) and mPD-L1(+) DLBCL were significantly associated with non-germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1(+) TILs was significantly higher in GCB-type tumors and lower in mPD-L1(-) and PD-L1(+) DLBCL. Patients with PD-L1(+) DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1(-) DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1(+) and mPD-L1(-) DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1(+) DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup.
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Hematology, Iizuka Hospital, Iizuka, Japan;
authors.forename: Junichi
authors.initials: J
authors.lastname: Kiyasu
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Akie
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Ayako
authors.initials: A
authors.lastname: Ichikawa
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.affiliation: Department of Hematology, Iizuka Hospital, Iizuka, Japan;
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yufu
authors.affiliation: Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; and.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Motoaki
authors.initials: M
authors.lastname: Shiratsuchi
authors.affiliation: Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D001706:Biopsy; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis; D012189:Retrospective Studies; D015996:Survival Rate; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor