Effects of PD‑1/PD‑L1 on the malignant behavior of thyroid cancer cells through the TGF‑β/Smad signaling pathway

Papillary thyroid cancer (PTC) is the most common type of malignant tumor in the endocrine system, with an incidence rate that is increasing year by year. In addition, the mortality rate of advanced PTC is also on the rise, posing a threat to human health. Programmed cell death protein‑1 (PD‑1)/programmed death‑ligand 1 (PD‑L1) signaling has been reported to be abnormally expressed in PTC, while the possible effects and underlying mechanisms remain to be further explored. In the present study, the expression levels of PD‑1 and PD‑L1 were upregulated in clinical PTC tissues as well as TPC‑1 and BCPAP cells as detected by reverse transcription‑quantitative PCR and western blotting analysis. Notably, PD‑1 expression in tissue samples may originate from both tumor cells and tumor‑infiltrating immune cells, whereas PD‑1 detected in cell lines solely represents tumor‑intrinsic expression. Functionally, downregulation of PD‑1 or PD‑L1 notably inhibited the viability, proliferation and induced the apoptosis of TC cells, as measured by Cell Counting Kit‑8, EdU, colony formation, flow cytometry and western blotting analysis. In addition, downregulation of PD‑1 or PD‑L1 markedly suppressed the migration, invasion and epithelial‑mesenchymal transition progress of TC cells, as measured by wound healing and Transwell migration and invasion assays, as well as western blotting analysis. Furthermore, downregulation of PD‑1 or PD‑L1 inactivated the TGF‑β/Smad signaling pathway. Exogenous TGF-β partially restored the effects of short hairpin (sh)‑PD‑1 or sh‑PD‑L1 on the viability, proliferation, apoptosis, migration, invasion and EMT progress of PTC cells. To conclude, the present study suggests PD‑1/PD‑L1 may represent potential therapeutic targets for the treatment of patients with PTC, though further studies across additional thyroid cancer subtypes are warranted.