Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells.

摘要: Rationale: STING is a critical player in the innate and adaptive immune system, sensing cytosolic DNA to activate expression of interferon genes regulate T lymphocytes, which drives immunogenic responses cancer cells. Tumor-associated macrophages (TAMs), abundantly present tumor microenvironment, play key role development. Gastric one most common leading causes cancer-related death worldwide. However, studies on function regulation TAMs their roles gastric progression are still limited. Methods: We analyzed CD68 200 pairs adjacent normal tissues by immunohistochemistry identify prognostic values STING, as well correlations between cancer. The characteristics STING-altered macrophages, effects cell apoptosis differentiation were examined flow cytometry. Cytokines secreted identified Human Inflammation Array3 kit. Concentrations soluble IL24 IFN-β measured ELISA. In vivo models, including spontaneous p53+/- mice line-based xenografts, established, clinical benefits examined. Results: Our study identifies factor for cancer, first time demonstrated that knocking-down activation 2'3'-c-GAMP both promote polarizing into pro-inflammatory subtype induce cells, mechanistically through IL6R-JAK-IL24 pathway. Conclusions : This evaluated targeting anti-gastric-cancer therapies. Moreover, we unveil novel pathway macrophages.