Epstein–Barr Virus LMP1 Induces Soluble PD-L1 in Nasopharyngeal Carcinoma
Kina Kase, Satoru Kondo, Naohiro Wakisaka, Hirotomo Dochi, Harue Mizokami, Eiji Kobayashi, Makoto Kano, Takeshi Komori, Nobuyuki Hirai, Takayoshi Ueno, Yosuke Nakanishi, Miyako Hatano, Kazuhira Endo, Makiko Moriyama‐Kita, Hisashi Sugimoto, Tomokazu Yoshizaki
Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy. The principal oncogene of EBV, latent membrane protein 1 (LMP1), induces the expression of programmed death-ligand 1 (PD-L1), which is an immunosuppressive transmembrane protein and a promising therapeutic target for various malignancies. Recent studies have revealed an association between the level of soluble PD-L1 (sPD-L1) and disease progression. However, the role of sPD-L1 in NPC or its relevance to LMP1 has not been elucidated. This study aimed to examine whether LMP1 induces sPD-L1 in vitro and analyze the clinical relevance of LMP1, PD-L1, and sPD-L1 in NPC patients. Analysis of nasopharyngeal cell lines revealed that LMP1 induces both cellular PD-L1 and sPD-L1. Analysis of biopsy specimens from 32 NPC patients revealed that LMP1 expression was significantly correlated with PD-L1 expression. Finally, the serum sPD-L1 level in NPC patients was higher than that in the controls. Moreover, the sPD-L1 level in the advanced stage was higher than that in the early stage. However, LMP1 expression, PD-L1 expression, and sPD-L1 levels were not associated with prognosis. These results suggest that LMP1 induces both sPD-L1 and PD-L1, which are associated with NPC progression.