Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma

Yuka Kozuma, Kazuki Takada, Gouji Toyokawa, Kenichi Kohashi, Mototsugu Shimokawa, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Yoshinao Oda, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. Results: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.

元の言語英語
ページ(範囲)20-29
ページ数10
ジャーナルEuropean Journal of Cancer
101
DOI
出版物ステータス出版済み - 9 2018

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CD274 Antigen
Indoleamine-Pyrrole 2,3,-Dioxygenase
Cell Death
Ligands
Multivariate Analysis
Adenocarcinoma of lung
Cell Line
Neoplasms
Transforming Growth Factors
Immunosuppressive Agents
Reverse Transcriptase Polymerase Chain Reaction
Interferons
Disease-Free Survival
Blood Vessels
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma. / Kozuma, Yuka; Takada, Kazuki; Toyokawa, Gouji; Kohashi, Kenichi; Shimokawa, Mototsugu; Hirai, Fumihiko; Tagawa, Tetsuzo; Okamoto, Tatsuro; Oda, Yoshinao; Maehara, Yoshihiko.

:: European Journal of Cancer, 巻 101, 09.2018, p. 20-29.

研究成果: ジャーナルへの寄稿記事

Kozuma, Yuka ; Takada, Kazuki ; Toyokawa, Gouji ; Kohashi, Kenichi ; Shimokawa, Mototsugu ; Hirai, Fumihiko ; Tagawa, Tetsuzo ; Okamoto, Tatsuro ; Oda, Yoshinao ; Maehara, Yoshihiko. / Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma. :: European Journal of Cancer. 2018 ; 巻 101. pp. 20-29.
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title = "Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma",
abstract = "Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. Results: IDO1 was expressed in 260 patients (60.9{\%}) at 1{\%} cut-off and 63 patients (14.8{\%}) at 50{\%} cut-off. Tissues from 145 patients (34.0{\%}) were positive for PD-L1 using the cut-off of 1{\%}. Multivariate analysis showed that ≥1{\%} IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8{\%}), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.",
author = "Yuka Kozuma and Kazuki Takada and Gouji Toyokawa and Kenichi Kohashi and Mototsugu Shimokawa and Fumihiko Hirai and Tetsuzo Tagawa and Tatsuro Okamoto and Yoshinao Oda and Yoshihiko Maehara",
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T1 - Indoleamine 2,3-dioxygenase 1 and programmed cell death-ligand 1 co-expression correlates with aggressive features in lung adenocarcinoma

AU - Kozuma, Yuka

AU - Takada, Kazuki

AU - Toyokawa, Gouji

AU - Kohashi, Kenichi

AU - Shimokawa, Mototsugu

AU - Hirai, Fumihiko

AU - Tagawa, Tetsuzo

AU - Okamoto, Tatsuro

AU - Oda, Yoshinao

AU - Maehara, Yoshihiko

PY - 2018/9

Y1 - 2018/9

N2 - Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. Results: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.

AB - Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive effector, and its expression is associated with prognosis in several cancer types. Here, we investigated the relationship between IDO1 expression in lung adenocarcinoma and patient prognosis and clinicopathological features, including programmed cell death-ligand 1 (PD-L1) expression. Materials and methods: In this study, surgically resected primary lung adenocarcinoma specimens from 427 patients were evaluated for IDO1 and PD-L1 expression by immunohistochemistry, and lung adenocarcinoma cell lines were evaluated for IDO1 and PD-L1 protein expression by enzyme-linked immunosorbent assay and flow cytometry and for messenger RNA levels by real-time reverse-transcriptase polymerase chain reaction analysis. Results: IDO1 was expressed in 260 patients (60.9%) at 1% cut-off and 63 patients (14.8%) at 50% cut-off. Tissues from 145 patients (34.0%) were positive for PD-L1 using the cut-off of 1%. Multivariate analysis showed that ≥1% IDO1 positivity was significantly associated with higher tumour grade, vascular invasion and PD-L1 expression. IDO1 and PD-L1 proteins were co-expressed in 123 patients (28.8%), and co-expressing tumours exhibited significantly more malignant traits than those positive for one or neither protein. In multivariate analysis, co-expression of IDO1 and PD-L1 was significantly associated with shorter disease-free survival and overall survival. Both proteins were upregulated in lung adenocarcinoma cell lines by treatment with interferon-γ and transforming growth factor-β. Conclusion: These results suggest that IDO1 and PD-L1 co-expression may define an aggressive form of lung adenocarcinoma.

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U2 - 10.1016/j.ejca.2018.06.020

DO - 10.1016/j.ejca.2018.06.020

M3 - Article

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JO - European Journal of Cancer and Clinical Oncology

JF - European Journal of Cancer and Clinical Oncology

SN - 0959-8049

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