Role of BTLA/HVEM network in development of gastric cancer

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.