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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2019

01-06-2019 | NSCLC | Translational Research and Biomarkers

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

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

Published in: Annals of Surgical Oncology | Issue 6/2019

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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.
Appendix
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Metadata
Title
A Clinicopathological and Prognostic Analysis of PD-L2 Expression in Surgically Resected Primary Lung Squamous Cell Carcinoma
Authors
Taichi Matsubara, MD
Kazuki Takada, MD, PhD
Koichi Azuma, MD, PhD
Shinkichi Takamori, MD, PhD
Gouji Toyokawa, MD, PhD
Akira Haro, MD, PhD
Atsushi Osoegawa, MD, PhD
Tetsuzo Tagawa, MD, PhD
Akihiko Kawahara, PhD
Jun Akiba, PhD
Isamu Okamoto, MD, PhD
Yoichi Nakanishi, MD, PhD
Yoshinao Oda, MD, PhD
Tomoaki Hoshino, MD, PhD
Yoshihiko Maehara, MD, PhD
Publication date
01-06-2019
Publisher
Springer International Publishing
Keywords
NSCLC
NSCLC
Published in
Annals of Surgical Oncology / Issue 6/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07257-3

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