Abstract
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. 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. 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. 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. Clin Cancer Res; 22(18); 4727-34. ©2016 AACR.
Highlights
Thymic epithelial tumors are the most common type of malignancy arising in the anterior mediastinum and include thymoma and thymic carcinoma; the latter is a relatively rare, high-grade malignancy that directly invades adjacent structures and undergoes distant metastasis
Compared with normal subjects, 3 thymic carcinoma patients showed an increase in Programmed death ligand 1 (PD-L1) copy number, whereas 8 did not
Here, for the first time, we report that PD-L1 and Programmed death 1 (PD-1) expression might be useful prognostic predictors in thymic carcinoma
Summary
Thymic epithelial tumors are the most common type of malignancy arising in the anterior mediastinum and include thymoma and thymic carcinoma; the latter is a relatively rare, high-grade malignancy that directly invades adjacent structures and undergoes distant metastasis. The most effective therapeutic modality for treating thymic carcinoma is surgical complete resection [1, 2], which increases the 5-year overall survival (OS) from 33.3%–65.0% to 53.0%–65.7% [3,4,5,6,7,8]. Thymic carcinoma is widely recognized to respond poorly to many chemotherapeutic agents, with an objective response rate of 20%–36%, concomitant administration of carboplatin and paclitaxel yields longer survival [9, 10]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/). There is a need for more effective therapeutic strategies, which requires detailed knowledge of underlying molecular oncogenic mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
