Background: The significance of epithelial-mesenchymal transition (EMT) and immune checkpoint proteins in thymic carcinoma remains unknown. We examined the clinical significance of EMT, tumor-infiltrating lymphocytes expressing the immune checkpoint protein, programmed cell death 1 (PD-1 + TILs), and the expression of PD-1 ligand 1 (PD-L1) in thymic carcinoma (TC). We also investigated the relationships between these immune checkpoint proteins and the EMT status and examined the impact of induction chemotherapy on patients with tumors that express these proteins.
Methods: The relationship between PD-1 + TILs/PD-L1 and clinicopathological findings including EMT was investigated by immunohistochemistry (IHC) of surgically resected samples from 43 patients with TC. In 15 patients receiving induction therapy (IT), those factors were compared before and after IT.
Results: With IHC, 26 cases (60.5%) were positive for PD-L1, and 19 cases were positive for PD-1 + TILs (44.2%). The disease-free survival rate in patients showing EMT and who were PD-1/PD-L1 positive was significantly worse compared to negative cases (EMT; P = 0.0095, PD-1; P = 0.001, PD-L1; P = 0.0037). We found a significant relationship between PD-L1 and EMT status (P = 0.01). In patients who received IT, PD-L1 increased, and the change was strongly correlated with EMT status (P = 0.01).
Conclusion: Epithelial-mesenchymal transition, PD-L1, and PD-1 + TILs have prognostic impact, and PD-L1 is correlated with EMT status. PD-L1 expression after IT was significantly higher compared to before IT and was correlated with the EMT change. Thus, PD-L1 may be upregulated during EMT, and anti-PD-1/PD-L1 immunotherapy may provide reliable treatment of TC in combination with chemotherapy.
Keywords: PD-1/PD-L1; TGF-β; epithelial-mesenchymal transition; induction therapy; thymic carcinoma.
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.