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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. Clin Cancer Res; 22(18); 4727–34. ©2016 AACR.

Key Points• PD-L1 expression in neoplastic cells or stromal cells is associated with poor or good prognosis in ATLL, respectively.• Distinction of expression pattern of PD-L1 might be important on the point of prognostic and therapeutic markers in ATLL. The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P 5 .0322 and P 5 .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL. (Blood. 2016;128(10):1374-1381

Epitaxial Pb(Zr,Ti)O3(PZT) films, 1.5–2.0μm in thickness, with a Zr∕(Zr+Ti) ratio ranging from 0.20 to 0.75 were grown on (100)c-,(110)c-, and (111)c-oriented SrRuO3∕∕SrTiO3 substrates at 600 °C by metal-organic chemical vapor deposition (MOCVD). The effects the Zr∕(Zr+Ti) ratio had on the crystal structure, dielectric and ferroelectric properties, and piezoelectric response of these films with different crystal orientations were systematically investigated. We ascertained from x-ray-diffraction reciprocal-space-mapping analysis that (001)T-∕(100)T-∕(100)R-,(101)T-∕(110)T-∕(110)R-∕(101¯)R-, and (111)T-∕(111)R-∕(111¯)R-oriented films had epitaxially grown on the respective (100)c-,(110)c-, and (111)c-oriented SrRuO3∕∕SrTiO3 substrates. The constituent phase changed from a tetragonal single phase, a mixture phase of a tetragonal and rhombohedral, to a rhombohedral single phase with increasing Zr∕(Zr+Ti) ratio irrespective of the orientation of the substrates. However, the range of the Zr∕(Zr+Ti) ratio of the film with the mixture phase differed depending on crystal orientation. This suggests that the stress relaxation process applied from the substrates changed due to crystal orientation. The relative dielectric constant was maximum for films with the mixture phase regardless of the crystal orientation. Remanent polarization was also maximum for these films on the (111)cSrRuO3∕∕SrTiO3 substrates, while it was minimum on the (100)c- and (110)c-oriented SrRuO3∕∕SrTiO3 substrates. Films with two phases coexisting had larger electric-field-induced strain than films with a single tetragonal or rhombohedral phase for the (111)-oriented films, but there were no remarkable changes in the (100)- and (110)-oriented films. Small ac signal measurements suggested that domain-wall motions easily occurred in the (111)-oriented films with the mixture phase compared with other orientations. These results indicated that the larger field-induced strain of the (111)-oriented PZT films consisting of a mixture of tetragonal and rhombohedral phases largely contributed to extrinsic factors such as domain-wall motions and phase transformation due to the applied electric field.