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Blood. 2015 Nov 5;126(19):2193-201. doi: 10.1182/blood-2015-02-629600. Epub 2015 Aug 3.

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma.

Author information

1
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;
2
Department of Pathology, Kurume University, School of Medicine, Kurume, Japan;
3
Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
4
Department of Hematology, Iizuka Hospital, Iizuka, Japan;
5
Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;
6
Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; and.
7
Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan.
8
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;

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.

PMID:
26239088
PMCID:
PMC4635115
DOI:
10.1182/blood-2015-02-629600
[Indexed for MEDLINE]
Free PMC Article
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