A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma

Taichi Matsubara, Kazuki Takada, Koichi Azuma, Shinkichi Takamori, Gouji Toyokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Background: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. Patients and Methods: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3 + , CD4 + , and CD8 + tumor-infiltrating lymphocytes were also examined. Results: The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. Conclusions: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.

元の言語英語
ページ(範囲)1925-1933
ページ数9
ジャーナルAnnals of Surgical Oncology
26
発行部数6
DOI
出版物ステータス出版済み - 6 15 2019

Fingerprint

Squamous Cell Carcinoma
Ligands
Lung
CD274 Antigen
Immunotherapy
Biomarkers
Immunohistochemistry
Tumor-Infiltrating Lymphocytes
Therapeutic Uses
Survival Analysis
Neoplasms
Cell Death

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

これを引用

A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma. / Matsubara, Taichi; Takada, Kazuki; Azuma, Koichi; Takamori, Shinkichi; Toyokawa, Gouji; Haro, Akira; Osoegawa, Atsushi; Tagawa, Tetsuzo; Kawahara, Akihiko; Akiba, Jun; Okamoto, Isamu; Nakanishi, Yoichi; Oda, Yoshinao; Hoshino, Tomoaki; Maehara, Yoshihiko.

:: Annals of Surgical Oncology, 巻 26, 番号 6, 15.06.2019, p. 1925-1933.

研究成果: ジャーナルへの寄稿記事

Matsubara, T, Takada, K, Azuma, K, Takamori, S, Toyokawa, G, Haro, A, Osoegawa, A, Tagawa, T, Kawahara, A, Akiba, J, Okamoto, I, Nakanishi, Y, Oda, Y, Hoshino, T & Maehara, Y 2019, 'A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma', Annals of Surgical Oncology, 巻. 26, 番号 6, pp. 1925-1933. https://doi.org/10.1245/s10434-019-07257-3
Matsubara, Taichi ; Takada, Kazuki ; Azuma, Koichi ; Takamori, Shinkichi ; Toyokawa, Gouji ; Haro, Akira ; Osoegawa, Atsushi ; Tagawa, Tetsuzo ; Kawahara, Akihiko ; Akiba, Jun ; Okamoto, Isamu ; Nakanishi, Yoichi ; Oda, Yoshinao ; Hoshino, Tomoaki ; Maehara, Yoshihiko. / A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma. :: Annals of Surgical Oncology. 2019 ; 巻 26, 番号 6. pp. 1925-1933.
@article{6c43d06933e24a2aaba4013f7de644cd,
title = "A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma",
abstract = "Background: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. Patients and Methods: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3 + , CD4 + , and CD8 + tumor-infiltrating lymphocytes were also examined. Results: The rates of positive PD-L2 expression were 77.3{\%} and 67.3{\%} using 5{\%} and 10{\%} cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5{\%} cut-off and p = 0.0500 at 10{\%} cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. Conclusions: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.",
author = "Taichi Matsubara and Kazuki Takada and Koichi Azuma and Shinkichi Takamori and Gouji Toyokawa and Akira Haro and Atsushi Osoegawa and Tetsuzo Tagawa and Akihiko Kawahara and Jun Akiba and Isamu Okamoto and Yoichi Nakanishi and Yoshinao Oda and Tomoaki Hoshino and Yoshihiko Maehara",
year = "2019",
month = "6",
day = "15",
doi = "10.1245/s10434-019-07257-3",
language = "English",
volume = "26",
pages = "1925--1933",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",
number = "6",

}

TY - JOUR

T1 - A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma

AU - Matsubara, Taichi

AU - Takada, Kazuki

AU - Azuma, Koichi

AU - Takamori, Shinkichi

AU - Toyokawa, Gouji

AU - Haro, Akira

AU - Osoegawa, Atsushi

AU - Tagawa, Tetsuzo

AU - Kawahara, Akihiko

AU - Akiba, Jun

AU - Okamoto, Isamu

AU - Nakanishi, Yoichi

AU - Oda, Yoshinao

AU - Hoshino, Tomoaki

AU - Maehara, Yoshihiko

PY - 2019/6/15

Y1 - 2019/6/15

N2 - Background: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. Patients and Methods: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3 + , CD4 + , and CD8 + tumor-infiltrating lymphocytes were also examined. Results: The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. Conclusions: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.

AB - Background: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. Patients and Methods: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3 + , CD4 + , and CD8 + tumor-infiltrating lymphocytes were also examined. Results: The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. Conclusions: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.

UR - http://www.scopus.com/inward/record.url?scp=85062488382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062488382&partnerID=8YFLogxK

U2 - 10.1245/s10434-019-07257-3

DO - 10.1245/s10434-019-07257-3

M3 - Article

C2 - 30815803

AN - SCOPUS:85062488382

VL - 26

SP - 1925

EP - 1933

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

IS - 6

ER -