Yu-Feng Wei1, Chang-Yao Chu2, Chao-Chun Chang3, Sheng-Hsiang Lin4, Wu-Chou Su5, Yau-Lin Tseng3, Chien-Chung Lin6, Yi-Ting Yen7. 1. Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan. 2. Division of Surgical Pathology, Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3. Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 4. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 5. Division of Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 6. Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 7. Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Trauma and Acute Care Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: b85401067@gmail.com.
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.
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%) thymomapatients, 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.
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