MAST CELL STING ACTIVATION IN INFECTION AND CANCER IMMUNITY

Abstract

Mast cells (MCs) are long-lived, tissue-resident immune cells essential for host defense. The STING pathway, a key innate immune response to infection and cellular stress, promotes strong type I interferon (IFN) and pro-inflammatory responses. While the STING pathway holds therapeutic potential in cancer and infection, its role in MCs remains underexplored. Our study demonstrates that MCs trigger type I IFN and NF-κB responses upon STING activation. We show that MCs are susceptible to Shigella flexneri infection, leading to an upregulation of type I IFN and interferon-stimulated gene expression, partially dependent on STING. In a murine ovarian cancer model, MC deficiency led to longer survival, whereas reconstituted MC-deficient mice surprisingly showed improved survival. Treatment with a STING agonist increased survival, but overexpressing STING in MCs within tumors provided no additional benefit. These findings offer valuable insights into STING-mediated immunity in MCs and highlight potential avenues for future therapeutic exploration.