Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma

• Published in: Clinical cancer research 2016-09, Vol.22 (18), p.4727-4734
• Main Authors: Yokoyama, Shintaro, Miyoshi, Hiroaki, Nakashima, Kazutaka, Shimono, Joji, Hashiguchi, Toshihiro, Mitsuoka, Masahiro, Takamori, Shinzo, Akagi, Yoshito, Ohshima, Koichi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor; Carcinoma - diagnosis; Carcinoma - genetics; Carcinoma - mortality; Carcinoma - therapy; Female; Gene Dosage; Gene Expression; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymphocyte Count; Male; Middle Aged; Neoplasm Staging; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Thymus Neoplasms - diagnosis; Thymus Neoplasms - genetics; Thymus Neoplasms - mortality; Thymus Neoplasms - therapy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-16-0434

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.