Oral cancer is a fatal disease, which accounts for the fourth highest incidence of malignancy in males and the seventh highest in the general population of Taiwan. Oral cancer is increasing in Taiwan. About 95% of oral cancer in Taiwan is oral squamous cell carcinoma (OSCC). With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for treatment of head and neck cancer. The PD-1/PD-L1 checkpoint is a critical regulator of activated T cell-cancer cell interactions which defend tumor cells against immune surveillance. Thyroid hormone induces PD-L1 expression in human oral cancer cells. Human oral cancer OEC-M1 and SCC-25 cells were treated with different concentrations of T4 (10-8 to 10-6M) for 24 h and cells were harvested and total RNA was extracted. qPCR of PD-L1 revealed that PD-L1 mRNA was significantly induced by thyroid hormone on a concentration-dependent basis. Parallel studies were conducted to study the effect of thyroid hormone on PD-L1 protein accumulation. Cancer cells were treated with different concentrations of T4 for 24 h. Total proteins were extracted and western blot analysis of PD-L1 was conducted. Thyroid hormone-activated ERK1/2 and STAT3 were companied with PD-L1 expression. Inhibition of ERK1/2 and consequently STAT3 activation also blocked PD-L1 induced by thyroid hormone. Knockdown of PD-L1 expression by siRNA also inhibits thyroid hormone-induced proliferation of oral cancer cells which indicated that PD-L1 expression is involved in thyroid hormone-induced cancer growth via an ERK1/2-STAT3 signal transduction pathway in oral cancer cells.

Citation Format: Yu-Tang Chin, Kwan-Wei Su, Yee-Tang Lim, Ya-Jung Shih, Yi-Ru Chen, Sheng-Yang Lee, Paul J. Davis, Hung-Yun Lin, Earl Fu. Thyroid hormone induces PD-L1 expression in oral cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4551.