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

研究成果: ジャーナルへの寄稿記事

192 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)2193-2201
ページ数9
ジャーナルBlood
126
発行部数19
DOI
出版物ステータス出版済み - 11 5 2015

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Lymphoma, Large B-Cell, Diffuse
Cell death
Cell Death
Cells
Ligands
Survival
Tumors
CD274 Antigen
Tumor-Infiltrating Lymphocytes
Tumor Microenvironment
Lymphocytes
B-Lymphocytes
Neoplasms
Germinal Center
Biopsy
Human Herpesvirus 4
Viruses
Immunotherapy

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

これを引用

Kiyasu, J., Miyoshi, H., Hirata, A., Arakawa, F., Ichikawa, A., Niino, D., ... 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

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. / Kiyasu, Junichi; Miyoshi, Hiroaki; Hirata, Akie; Arakawa, Fumiko; Ichikawa, Ayako; Niino, Daisuke; Sugita, Yasuo; Yufu, Yuji; Choi, Ilseung; Abe, Yasunobu; Uike, Naokuni; Nagafuji, Koji; Okamura, Takashi; Akashi, Koichi; Takayanagi, Ryoichi; Shiratsuchi, Motoaki; Ohshima, Koichi.

:: Blood, 巻 126, 番号 19, 05.11.2015, p. 2193-2201.

研究成果: ジャーナルへの寄稿記事

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, 巻. 126, 番号 19, pp. 2193-2201. https://doi.org/10.1182/blood-2015-02-629600
Kiyasu, Junichi ; Miyoshi, Hiroaki ; Hirata, Akie ; Arakawa, Fumiko ; Ichikawa, Ayako ; Niino, Daisuke ; Sugita, Yasuo ; Yufu, Yuji ; Choi, Ilseung ; Abe, Yasunobu ; Uike, Naokuni ; Nagafuji, Koji ; Okamura, Takashi ; Akashi, Koichi ; Takayanagi, Ryoichi ; Shiratsuchi, Motoaki ; Ohshima, Koichi. / Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. :: Blood. 2015 ; 巻 126, 番号 19. pp. 2193-2201.
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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.",
author = "Junichi Kiyasu and Hiroaki Miyoshi and Akie Hirata and Fumiko Arakawa and Ayako Ichikawa and Daisuke Niino and Yasuo Sugita and Yuji Yufu and Ilseung Choi and Yasunobu Abe and Naokuni Uike and Koji Nagafuji and Takashi Okamura and Koichi Akashi and Ryoichi Takayanagi and Motoaki Shiratsuchi and Koichi Ohshima",
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T1 - Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

AU - Kiyasu, Junichi

AU - Miyoshi, Hiroaki

AU - Hirata, Akie

AU - Arakawa, Fumiko

AU - Ichikawa, Ayako

AU - Niino, Daisuke

AU - Sugita, Yasuo

AU - Yufu, Yuji

AU - Choi, Ilseung

AU - Abe, Yasunobu

AU - Uike, Naokuni

AU - Nagafuji, Koji

AU - Okamura, Takashi

AU - Akashi, Koichi

AU - Takayanagi, Ryoichi

AU - Shiratsuchi, Motoaki

AU - Ohshima, Koichi

PY - 2015/11/5

Y1 - 2015/11/5

N2 - 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.

AB - 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.

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