The LGALS9/miR-491-5p Axis Regulates CD8⁺ T Cell Function and Inhibits the Progression of Gastric Cancer

Gastric cancer is a prevalent and clinically significant gastrointestinal malignancy worldwide. Gastric cancer is characterized by limited treatment efficacy and a high recurrence rate. In this study, we found that LGALS9 was highly expressed in gastric cancer and may contribute to disease progression by modulating the infiltration of CD8⁺ T cells. Genetic knockout of LGALS9 reversed T cell function, attenuated immunosuppression, and enhanced the cytotoxic activity of T cells to kill gastric cancer cells. Furthermore, miR-491-5p was identified as a potential suppressor in gastric cancer. The microRNA miR-491-5p regulated T cell-mediated immunity by targeting and inhibiting LGALS9, which was similar to the effect of LGALS9 knockout. Overall, the key target LGALS9 and its inhibitor miR-491-5p represent promising potential for treating gastric cancer.