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

Junichi Kiyasu, Hiroaki Miyoshi, Akie Hirata, Fumiko Arakawa, Ayako Ichikawa, Daisuke Niino, Yasuo Sugita, Yuji Yufu, Ilseung Choi, Yasunobu Abe, Naokuni Uike, Koji Nagafuji, Takashi Okamura, Koichi Akashi, Ryoichi Takayanagi, Motoaki Shiratsuchi, Koichi Ohshima

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223 Citations (Scopus)

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-11 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-11 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 5 .0009). In contrast, there was no significant difference in OS betweenmPD-L1+ andmPD-L1-DLBCL(P5.31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P 5 .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.

Original languageEnglish
Pages (from-to)2193-2201
Number of pages9
JournalBlood
Volume126
Issue number19
DOIs
Publication statusPublished - Nov 5 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kiyasu, J., Miyoshi, H., Hirata, A., Arakawa, F., Ichikawa, A., Niino, D., Sugita, Y., Yufu, Y., Choi, I., Abe, Y., Uike, N., Nagafuji, K., Okamura, T., Akashi, K., Takayanagi, R., Shiratsuchi, M., & Ohshima, K. (2015). Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood, 126(19), 2193-2201. https://doi.org/10.1182/blood-2015-02-629600