Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Ann Surg Oncol. 2019 Jun;26(6):1925-1933. doi: 10.1245/s10434-019-07257-3. Epub 2019 Feb 27.
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.
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.
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.
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.
针对程序性细胞死亡蛋白-1（PD-1）和程序性死亡配体 1（PD-L1）的免疫疗法已显示出对肺鳞状细胞癌（SCC）的显著治疗效果，并且 PD-L1 表达不仅是对免疫疗法反应的预测生物标志物，也是肺 SCC 的预后因素。然而，另一种 PD-1 配体程序性死亡配体 2（PD-L2）的临床意义仍不清楚。因此，我们通过免疫组织化学分析了手术切除的原发性肺 SCC 中的 PD-L2 表达。
通过免疫组织化学分析了 211 例原发性肺 SCC 标本中肿瘤细胞上的 PD-L1 和 PD-L2 表达。此外，还检查了 CD3、CD4 和 CD8 肿瘤浸润淋巴细胞的数量。
分别使用 5%和 10%截断值，PD-L2 表达阳性率分别为 77.3%和 67.3%。肿瘤细胞中低 PD-L2 表达与组织学类型（非角化/角化）和淋巴管浸润有关。PD-L2 阳性患者的术后生存时间明显更长（对数秩检验；在 5%截断值时 p=0.0170，在 10%截断值时 p=0.0500）。此外，根据 PD-L1 和 PD-L2 表达进行的生存分析表明，PD-L1 阳性和 PD-L2 阴性患者的预后最差。
PD-L2 蛋白表达与原发性肺 SCC 患者的预后相关。PD-L2 表达可能是 PD-1/PD-L1 靶向免疫疗法反应的潜在生物标志物，应在未来的研究中进行调查。
