Abstract 2665: Green tea catechin, EGCG, enhances antitumor immunity by down-regulation of PD-L1 expression in non-small human lung cancer cell lines

Abstract

Abstract (-)-Epigallocatechin gallate (EGCG) is now widely accepted as a non-toxic, effective cancer preventive compound. EGCG also acts as a synergist with anti-cancer drugs for cancer treatment. Considering the wide beneficial effects of EGCG, we think EGCG might have antitumor immunity. Programmed death-ligand 1 (PD-L1) expression on tumor cells is involved in PD-L1/PD-1 pathway. PD-L1 protein levels varied among 6 non-small human lung cancer cell lines (NSCLCs): LC-AI and Lu99 cell lines showed the highest PD-L1 expression, A549 and H322 cell lines were medium, and H1703 and H1299 were very low, independent on cancer cell lines. Since PD-L1 expression is induced by various cytokines and growth factors, we studied the effects of IFN-γ and EGF on cell-surface PD-L1 level using flow cytometry, and its gene expression using RT-PCR. Treatment with IFN-γ dose-dependently stimulated PD-L1 expression in both A549 and H1299 cells, and not effective on Lu99 cells, whereas treatment with EGF stimulated PD-L1 in Lu99 cells only. Pretreatment with EGCG for 3 h, dose-dependently inhibited INF-γ-induced PD-L1 gene expression and protein level on cell-surface in both A549 and H1299. It is important to note that EGCG also inhibited phosphorylation of STAT1. In addition, EGCG inhibited EGF-induced PD-L1 gene expression and protein level in Lu99 cells via inhibition of phosphorylation of Akt. In order to study the effects of EGCG in between rodent carcinogenesis experiment and antitumor immunity, green tea extract (GTE) was given to NNK-induced lung tumors in A/J mice, which showed significant reduction of PD-L1 protein level, determined by immunohistochemical analysis using anti-PD-L1 antibody. Furthermore, the group treated with NNK + GTE significantly showed reduced number of tumors per mouse from 3.2 to 2.2, and decreased tumor size. Treatment with Wortmannin, a PI3K inhibitor, as a control, did not inhibit PD-L1 expression in A549 and H1299 cells. The results strongly suggest that EGCG enhances antitumor immunity via inhibition of PD-L1 expression in cancer cells, resulting in significant cancer preventive activity. Citation Format: Anchalee Rawangkan, Keisuke Iida, Ryo Sakai, Hirota Fujiki, Masami Suganuma. Green tea catechin, EGCG, enhances antitumor immunity by down-regulation of PD-L1 expression in non-small human lung cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2665. doi:10.1158/1538-7445.AM2017-2665