Kase Kina, Kondo Satoru, Wakisaka Naohiro, Dochi Hirotomo, Mizokami Harue, Kobayashi Eiji, Kano Makoto, Komori Takeshi, Hirai Nobuyuki, Ueno Takayoshi, Nakanishi Yosuke, Hatano Miyako, Endo Kazuhira, Moriyama-Kita Makiko, Sugimoto Hisashi, Yoshizaki Tomokazu
Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan.
Microorganisms. 2021 Mar 15;9(3):603. doi: 10.3390/microorganisms9030603.
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.
鼻咽癌（NPC）是一种与爱泼斯坦-巴尔病毒（EBV）相关的恶性肿瘤。EBV的主要致癌基因，潜伏膜蛋白1（LMP1），可诱导程序性死亡配体1（PD-L1）的表达，PD-L1是一种免疫抑制性跨膜蛋白，也是各种恶性肿瘤的一个有前景的治疗靶点。最近的研究揭示了可溶性PD-L1（sPD-L1）水平与疾病进展之间的关联。然而，sPD-L1在NPC中的作用或其与LMP1的相关性尚未阐明。本研究旨在检测LMP1在体外是否诱导sPD-L1，并分析LMP1、PD-L1和sPD-L1在NPC患者中的临床相关性。对鼻咽癌细胞系的分析表明，LMP1可诱导细胞PD-L1和sPD-L1。对32例NPC患者活检标本的分析显示，LMP1表达与PD-L1表达显著相关。最后，NPC患者血清sPD-L1水平高于对照组。此外，晚期患者的sPD-L1水平高于早期患者。然而，LMP1表达、PD-L1表达和sPD-L1水平与预后无关。这些结果表明，LMP1可诱导sPD-L1和PD-L1，它们与NPC进展相关。
