Shen Bo, Qian Aihua, Lao Wenji, Li Weiguang, Chen Xi, Zhang Benyan, Wang Huafeng, Yuan Fei, Sun Yunwei
Department of Gastroenterology of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Department of Pathology of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Cancer Manag Res. 2019 May 2;11:3909-3919. doi: 10.2147/CMAR.S203035. eCollection 2019.
Many studies have shown that programmed cell death protein 1 (PD-1) and its ligand, PD-L1, are expressed in advanced gastric cancer. Furthermore, detection of these proteins is associated with infiltrating CD8+ T-cells, indicating that an adaptive immune resistance mechanism occurs in advanced gastric cancer. However, PD-L1 and PD-1 expression in gastric intraepithelial neoplasia and early-stage gastric cancer (EGC) has yet to be elucidated. Fifty-four resections of low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC were stained by immunohistochemistry for PD-1, PD-L1, and CD8. CD8+ T-cell densities both within tumors and in the tumor-stromal interface were analyzed. Flow cytometry (FACS) was used to analyze the PD-1 expression in tumor tissues and peripheral blood mononuclear cells. Furthermore, the relationship between Helicobacter pylori (Hp) infection and PD-1 and PD-L1 was also evaluated. We demonstrated that PD-L1 expression was significantly increased in HGIN and EGC compared with LGIN, and both PD-1 and PD-L1 showed similar expression patterns, being mainly detected in infiltrating immune cells. FACS also showed that PD-1 was expressed on both CD4+ and CD8+ T-cells. However, no difference was found in CD8+ T-cell infiltration between LGIN and HGIN+EGC, and this was not not found to be associated with PD-L1 or PD-1 expression. However, Hp infection was significantly associated with expression of PD-L1 and PD-1. The PD-1/PD-L1 checkpoint is involved in intraepithelial neoplasia and EGC, but an adaptive immune resistance mechanism does not occur. Expression of PD-1/PD-L1 is also associated with Hp infection, and so Hp infection may be an important initiating factor. This study was approved by the Institutional Review Board of Ruijin Hospital and written informed consent was obtained from all patients.
许多研究表明,程序性细胞死亡蛋白1(PD - 1)及其配体PD - L1在进展期胃癌中表达。此外,这些蛋白的检测与浸润性CD8 + T细胞相关,表明进展期胃癌中存在适应性免疫抵抗机制。然而,胃上皮内瘤变和早期胃癌(EGC)中PD - L1和PD - 1的表达情况尚未阐明。对54例低级别上皮内瘤变(LGIN)、高级别上皮内瘤变(HGIN)和EGC切除标本进行免疫组织化学染色,检测PD - 1、PD - L1和CD8。分析肿瘤内及肿瘤-基质界面处CD8 + T细胞密度。采用流式细胞术(FACS)分析肿瘤组织和外周血单个核细胞中PD - 1的表达。此外,还评估了幽门螺杆菌(Hp)感染与PD - 1和PD - L1之间的关系。我们发现,与LGIN相比,HGIN和EGC中PD - L1表达显著增加,且PD - 1和PD - L1表现出相似的表达模式,主要在浸润性免疫细胞中检测到。FACS还显示PD - 1在CD4 +和CD8 + T细胞上均有表达。然而,LGIN与HGIN + EGC之间CD8 + T细胞浸润无差异,且未发现其与PD - L1或PD - 1表达相关。但是,Hp感染与PD - L1和PD - 1的表达显著相关。PD - 1/PD - L1免疫检查点参与上皮内瘤变和EGC,但不存在适应性免疫抵抗机制。PD - 1/PD - L1的表达也与Hp感染相关,因此Hp感染可能是一个重要的起始因素。本研究经瑞金医院伦理委员会批准,所有患者均签署书面知情同意书。
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