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: 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‐β (TGF‐β), and CD8(+) tumor‐infiltrating lymphocytes (CD8(+) TILs) in patients with TETs. METHODS: 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: Patients with advanced thymic carcinoma exhibited higher levels of PD‐L1 and TGF‐β than patients with advanced invasive thymic carcinoma (PD‐L1: 65.0% vs. 46.2%, P = 0.472; TGF‐β: 65.0% vs. 15.4%, P = 0.011). Five advanced thymic carcinoma patients with low levels of PD‐L1 and TGF‐β exhibited high levels of CD8 staining. The median OS was 29.5 months patients with high TGF‐β expression versus 62.9 in patients with low TGF‐β (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). CONCLUSIONS: Our results showed the prognostic roles of PD‐L1, TGF‐β, and CD8(+) TILs in patients with advanced TETs, and the potential for development of anti‐PD‐1/PD‐L1 therapies.