Tr1 responses are elevated in asymptomatic H. pylori-infected individuals and are functionally impaired in H. pylori-gastric cancer patients

Abstract Gastric cancer is one of the most lethal malignancies worldwide. Chronic Helicobacter pylori ( H. pylori ) infection can induce an inflammatory response that promotes atrophic gastritis, a preceding event to cancer development. The type 1 regulatory T (Tr1) cells have recently emerged as a critical participant in maintaining self-tolerance. In this study, we examined Tr1 cells in H. pylori infection and gastric cancer development. While H. pylori -uninfected (uninfected) subjects presented low Tr1 frequency in the peripheral blood, H. pylori -infected asymptomatic (infected) individuals and H. pylori -infected gastric cancer (cancer) individuals both presented elevated Tr1 frequency. Although the Tr1 cells from infected asymptomatic subjects were functionally more potent than those from uninfected healthy subjects, the Tr1 cells in cancer individuals demonstrated several functional impairments, such as reduced interleukin 10 (IL-10) expression, lower secretion of cytolytic factors including granzyme B and perforin, and lower capacity to suppress CD4 + CD25 - T cell and CD8 + T cell proliferation. In addition, the frequency and function of Tr1 cells were positively correlated with the disease-free survival of the gastric cancer patients. These results suggest that Tr1 cells might be involved in the regulating immune responses in H. pylori infection and gastric cancer development. The fact that Tr1 cells could suppress inflammation and produce cytotoxic molecules at the same time has made them attractive potential candidates for future immunotherapies.