Impact of PD-L1, transforming growth factor-β expression and tumor-infiltrating CD8 + T cells on clinical outcome of patients with advanced thymic epithelial tumors.

Background Methods Advanced thymic epithelial tumors (TETs) are indolent and poorly responsive to chemotherapy. PD-1/PD-L1 inhibitors have shown remarkable clinical benefit in several cancers; however, many immunomodulatory molecules have been identified that affect the immune response. This study examined the progonostic roles of PD-L1, transforming growth factor-beta (TGF-beta), and CD8(+) tumor-infiltrating lymphocytes (CD8(+) TILs) in patients with TETs. Retrospective analysis was performed on the data of 20 patients with stage IV thymic carcinoma and 13 with stage III/IV invasive thymoma. Tissue biopsies were obtained before first-line chemotherapy was administered. Protein levels were assessed by immunohistochemistry. Objective response rate, overall survival (OS), and progression-free survival (PFS) were analyzed. Results Conclusions Patients with advanced thymic carcinoma exhibited higher levels of PD-L1 and TGF-beta than patients with advanced invasive thymic carcinoma (PD-L1: 65.0% vs. 46.2%, P = 0.472; TGF-beta: 65.0% vs. 15.4%, P = 0.011). Five advanced thymic carcinoma patients with low levels of PD-L1 and TGF-beta exhibited high levels of CD8 staining. The median OS was 29.5 months patients with high TGF-beta expression versus 62.9 in patients with low TGF-beta (P = 0.052). In patients with advanced thymic carcinoma, the median PFS in the high PD-L1 expression group was 13.3 months versus 23.5 (P = 0.043) in the low PD-L1, and the median OS was 50.7 months in the high CD8 expression versus 15.1 in the CD8 low group (P = 0.154). Our results showed the prognostic roles of PD-L1, TGF-beta, and CD8(+) TILs in patients with advanced TETs, and the potential for development of anti-PD-1/PD-L1 therapies.