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

• Published in: Annals of surgical oncology 2019-06, Vol.26 (6), p.1925-1933
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers; CD3 antigen; CD4 antigen; CD8 antigen; Cell death; Immunohistochemistry; Immunotherapy; Ligands; Lung cancer; Lung carcinoma; Lymphocytes; Medical prognosis; Medicine; Medicine & Public Health; Oncology; PD-1 protein; PD-L1 protein; PD-L2 protein; Prognosis; Squamous cell carcinoma; Surgery; Surgical Oncology; Survival analysis; Translational Research and Biomarkers; Tumor cells; Tumor-infiltrating lymphocytes
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-019-07257-3

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.