Interferon‑γ induced PD‑L1 expression and soluble PD‑L1 production in gastric cancer
Yushi Imai, Tetsuhiro Chiba, Takayuki Kondo, Hiroaki Kanzaki, Kengo Kanayama, Junjie Ao, Ryuta Kojima, Yuko Kusakabe, Masato Nakamura, Tomoko Saito, Ryo Nakagawa, Eiichiro Suzuki, Shingo Nakamoto, Ryosuke Muroyama, Akinobu Tawada, Tomoaki Matsumura, Tomoo Nakagawa, Jun Kato, Ai Kotani, Hisahiro Matsubara, Naoya Kato
Abstract
Programmed death-ligand 1 (PD-L1) plays an essential role in tumor cell escape from anti-tumor immunity in various types of cancer, including gastric cancer (GC). The present study investigated the intracellular and membrane-bound expression of PD-L1 in the GC cell lines MKN1, MKN74, KATO III and OCUM-1. Furthermore, soluble PD-L1 (sPD-L1) level in the supernatant of GC cells and the serum of patients with GC and healthy controls was determined by ELISA. Interferon (IFN)-γ treatment of cells resulted in increased cytoplasmic expression of PD-L1 in GC cells in a dose-dependent manner, except for MKN74 cells; however, there was no association between tumor necrosis factor-α treatment and enhanced PD-L1 expression. Concordant with these findings, results from flow cytometry analysis demonstrated that membrane-bound PD-L1 expression was also increased following GC cell treatment with IFN-γ in a dose-dependent manner. In addition, significant sPD-L1 overproduction was observed only in the culture supernatant of OCUM-1 cells. Serum level of sPD-L1 was significantly increased in patients with GC, in particular in stage IV patients, compared with healthy controls. In conclusion, the present study demonstrated that IFN-γ treatment increased the intracellular and membrane-bound PD-L1 expression in GC cells. In addition, sPD-L1 was detected not only in the supernatant of GC cells but also in the serum of patients with GC. Further investigation on the underlying mechanism of regulation of PD-L1 expression and sPD-L1 production is required.