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27.02.2019 | Translational Research and Biomarkers

Prognostic Impact of Programmed Death-Ligand 2 Expression in Primary Lung Adenocarcinoma Patients

Annals of Surgical Oncology
PhD Shinkichi Takamori, PhD Kazuki Takada, PhD Koichi Azuma, MD Tomoko Jogo, PhD Mototsugu Shimokawa, PhD Gouji Toyokawa, PhD Fumihiko Hirai, PhD Tetsuzo Tagawa, PhD Akihiko Kawahara, PhD Jun Akiba, PhD Isamu Okamoto, PhD Yoichi Nakanishi, PhD Yoshinao Oda, PhD Tomoaki Hoshino, PhD Yoshihiko Maehara
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1245/​s10434-019-07231-z) contains supplementary material, which is available to authorized users.
Drs. Shinkichi Takamori and Kazuki Takada contributed equally to this work.

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Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients.


The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival.


Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018).


The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.

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Supplementary material 5 (DOCX 24 kb)
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