Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma
Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-16-0434
复制
发表时间：
2016-09-15
影响因子：
11.5
通讯作者：
Ohshima, Koichi
中科院分区：
文献类型：
--
作者：
Yokoyama, Shintaro;Miyoshi, Hiroaki;Ohshima, Koichi
目的：程序性死亡1/程序性死亡配体1（PD-1/PD-L1）通路的免疫检查点被认为在各种恶性肿瘤中逃避宿主抗肿瘤免疫监视中起重要作用;然而，对其在胸腺癌中的作用知之甚少。本研究探讨PD-1/PD-L1表达及其与临床病理特征、肿瘤浸润淋巴细胞（TIL）中免疫相关蛋白的表达以及患者预后的关系。实验设计：采用免疫组化方法对25例胸腺癌组织标本中PD-1和PD-1的表达进行评价。结果：与正常人相比，3例胸腺癌患者PD-L1基因拷贝数增加，8例胸腺癌患者PD-L1基因拷贝数未增加。与正常病例相比，PD-L1在拷贝数增加的病例中显著过表达。与低表达病例相比，PD-L1高表达与更高的无病生存率和总生存率相关。预后分析显示，PD-L1低表达和PD-1（+）TIL数量高是生存率差的重要预测因素，以及Masaoka-Koga IVa/IVb期疾病和不完全切除。在TILs的定量分析中，PD-L1表达与浸润CTLs的数量成比例相关。结论：在这里，我们首次报道，PD-L1和PD-1表达可能是胸腺癌有用的预后预测因子。预计进一步的研究将证实PD-L1和PD-1表达的预后价值，以及通过免疫治疗靶向PD-1/PD-L1通路在胸腺癌中的潜在疗效。（C）2016年AACR。
Purpose: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis.Experimental Design: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR.Results: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1(+) TILs as significant predictors of poor survival, together with Masaoka-Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs.Conclusions: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. (C)2016 AACR.