Different pattern of PD-L1, IDO, and FOXP3 Tregs expression with survival in thymoma and thymic carcinoma

Abstract

Objectives: The expression of immune checkpoint ligand PD-L1 has been reported in various tumors. The expression of IDO and FOXP3 Tregs are considered to be associated with tumor-induced tolerance and poor outcome. Their prognostic role in surgically treated thymoma and thymic carcinoma, however, has not been investigated.

Materials and methods: Tissue microarray (TMA) blocks comprised of 100 surgically treated thymomas and 69 surgically treated thymic carcinomas were conducted. Tissue sections were incubated with primary antibodies against PD-L1 (clone E1L3N, 1:100), IDO (clone 10.1, 1:50), and FOXP3 (clone 236 A/E7, 1:50). Comparisons for categorical variables were performed using χ² test and Fisher's exact test. Survival analysis was established using Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using Cox regression model.

Results and conclusions: High expression of PD-L1, IDO, and FOXP3 Tregs were identified in 36 (36%), 13 (13%), and 16 (16%) thymoma patients, respectively. High expression of PD-L1, IDO, and FOXP3 Tregs was associated with higher grade of tumor histology (P < 0.001, P = 0.007, and 0.014, respectively). High expression of PD-L1 was also associated with advanced Masaoka staging (P < 0.001). In patients with thymic carcinoma, high expression of PD-L1, IDO, and FOXP3 Tregs were identified in 25 (36%), 10 (14%), and 20 (29%) patients, respectively. Complete resection, low expression of IDO, and high expression of FOXP3 Tregs were associated with better overall survival (P = 0.001, 0.004, and 0.032, respectively), and progression-free survival (P < 0.001, P = 0.026, and 0.047, respectively) in multivariate analysis. In surgically treated thymoma, high PD-L1 expression was associated with advanced Masaoka staging. High PD-L1, IDO, and FOXP3 Tregs expression was associated with high grade histology. In surgically treated thymic carcinoma, significant survival benefit was noted in patients with complete resection, low IDO expression, and high FOXP3 Tregs expression.

Keywords: FOXP3; IDO; PD-L1; Thymic carcinoma; Thymoma.