Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential targets of novel combination therapy

Kazuki Takada, Kenichi Kouhashi, Mototsugu Shimokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Takashi Seto, Yoshinao Oda, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Objectives: Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). Materials and methods: The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry. Results: Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively). Conclusions: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.

元の言語英語
ページ(範囲)26-32
ページ数7
ジャーナルLung Cancer
128
DOI
出版物ステータス出版済み - 2 1 2019

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CD274 Antigen
Indoleamine-Pyrrole 2,3,-Dioxygenase
Squamous Cell Carcinoma
Lung
Therapeutics
Non-Small Cell Lung Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

これを引用

Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma : Potential targets of novel combination therapy. / Takada, Kazuki; Kouhashi, Kenichi; Shimokawa, Mototsugu; Haro, Akira; Osoegawa, Atsushi; Tagawa, Tetsuzo; Seto, Takashi; Oda, Yoshinao; Maehara, Yoshihiko.

:: Lung Cancer, 巻 128, 01.02.2019, p. 26-32.

研究成果: ジャーナルへの寄稿記事

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title = "Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential targets of novel combination therapy",
abstract = "Objectives: Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). Materials and methods: The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry. Results: Among 202 patients, 176 (87.1{\%}) were positive for IDO1 expression, 106 (52.5{\%}) were positive for PD-L1 expression, and 99 (49.0{\%}) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively). Conclusions: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.",
author = "Kazuki Takada and Kenichi Kouhashi and Mototsugu Shimokawa and Akira Haro and Atsushi Osoegawa and Tetsuzo Tagawa and Takashi Seto and Yoshinao Oda and Yoshihiko Maehara",
year = "2019",
month = "2",
day = "1",
doi = "10.1016/j.lungcan.2018.12.008",
language = "English",
volume = "128",
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journal = "Lung Cancer",
issn = "0169-5002",
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TY - JOUR

T1 - Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma

T2 - Potential targets of novel combination therapy

AU - Takada, Kazuki

AU - Kouhashi, Kenichi

AU - Shimokawa, Mototsugu

AU - Haro, Akira

AU - Osoegawa, Atsushi

AU - Tagawa, Tetsuzo

AU - Seto, Takashi

AU - Oda, Yoshinao

AU - Maehara, Yoshihiko

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Objectives: Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). Materials and methods: The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry. Results: Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively). Conclusions: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.

AB - Objectives: Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). Materials and methods: The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry. Results: Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher's exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P = 0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P = 0.0122, P = 0.0303 and P = 0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student's t-test: P = 0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher's exact test: P = 0.0033, P = 0.0003, and P < 0.0001, respectively). Conclusions: IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.

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