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Objectives:  Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression.   Patients and Methods:  A tissue microarray was constructed using 368 samples of TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations with clinicopathologic characteristics were analyzed. PD-L1 high  was designated as ≥50% of tumor proportion score; PD-1 high  and CD8 high  were defined as ≥5% and 1% of tumoral immune cells, respectively.   Results:  The cohort consisted of 308 patients with thymomas and 60 patients with TC. PD-L1 positivity was identified in 90.6% (328/362, ≥1%) of TETs, PD-1 expression of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ≥1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1 high ). The PD-L1 high  thymoma group was correlated with high Masaoka-Koga stage ( p  < 0.001), type B3 histology ( p  < 0.001), and myasthenia gravis ( p  < 0.001). This group exhibited poor overall survival (OS,  p  = 0.003, log-rank) and worse disease-free survival (DFS,  p  = 0.042, log-rank). No survival differences were detected between PD-L1 high  and PD-L1 low  groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1 high  expression was an independent poor prognostic factor ( p  = 0.047, HR 2.087, 95% CI, 1.009–4.318) in thymomas.   Conclusions:  To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.

frontiers in oncology

Clinicopathologic Significance and Immunogenomic Analysis of Programmed Death-Ligand 1 (PD-L1) and Programmed Death 1 (PD-1) Expression in Thymic Epithelial Tumors