Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center,Faculty of Medicine , Mazandaran University of Medical Sciences, Sari, Iran.
Hum Immunol. 2022 Aug-Sep;83(8-9):637-644. doi: 10.1016/j.humimm.2022.07.003. Epub 2022 Jul 30.
The immunopathological mechanism underlying intestinal metaplasia and gastric cancer remain incompletely understood. Regarding the role of B- and T-lymphocyte attenuator (BTLA) / herpesvirus entry mediator (HVEM) in tumorigenesis, this research was conducted to determine the BTLA/HVEM expression in development of gastric cancer. Gastric biopsy and peripheral blood was drawn from 32 non-ulcer dyspepsia (NUD) as control group, 19 intestinal metaplasia (IM), and 63 gastric cancer (GC). BTLA/HVEM expression were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. Soluble HVEM (sHVEM) and anti-Helicobacter pylori IgG antibody were assessed by ELISA. Our result showed that BTLA mRNA and protein were significantly increased in advanced stages of gastric cancer. HVEM was higher only at the protein level in the GC group. The sHVEM concentration was also higher in the GC group than in the NUD groups. In addition, we observed H. pylori-positive samples had a lower H-score of HVEM than H. pylori-negative ones. These results suggest that BTLA/HVEM/sHVEM inhibitory pathway is involved in immune regulation and progression of gastric cancer. Therefore, this inhibitory pathway might be a therapeutic target to further immunotherapy of gastric cancer.
肠上皮化生和胃癌的免疫病理机制尚不完全清楚。关于 B 和 T 淋巴细胞衰减因子（BTLA）/疱疹病毒进入介质（HVEM）在肿瘤发生中的作用，本研究旨在确定 BTLA/HVEM 在胃癌发展中的表达。从 32 例非溃疡性消化不良（NUD）作为对照组、19 例肠上皮化生（IM）和 63 例胃癌（GC）中抽取胃活检和外周血。通过免疫组织化学和实时定量聚合酶链反应分析 BTLA/HVEM 的表达。通过 ELISA 评估可溶性 HVEM（sHVEM）和抗幽门螺杆菌 IgG 抗体。我们的结果表明，BTLA mRNA 和蛋白在胃癌的晚期阶段显著增加。HVEM 仅在 GC 组的蛋白水平升高。GC 组的 sHVEM 浓度也高于 NUD 组。此外，我们观察到 H. pylori 阳性样本的 HVEM H 评分低于 H. pylori 阴性样本。这些结果表明，BTLA/HVEM/sHVEM 抑制途径参与了胃癌的免疫调节和进展。因此，该抑制途径可能是进一步胃癌免疫治疗的治疗靶点。
