Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies.

ABSTRACT: Intracellular bacterial pathogens are distinctive tools for fighting cancer, as they can proliferate in tumors and deliver therapeutic payloads to the eukaryotic cytosol. Cytosol-dwelling bacteria have undergone extensive preclinical and clinical testing, yet the mechanisms of activating innate immunity in tumors are unclear. We report that phylogenetically distinct cytosolic pathogens, including Listeria, Rickettsia, and Burkholderia species, elicited anti-tumor responses in poorly immunogenic melanoma and lymphoma in mice. Although the bacteria required cytosolic access, anti-tumor responses were largely independent of the cytosolic sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), but instead required Toll-like receptor (TLR) signali

SUBMITTER: Danielson M 

PROVIDER: S-EPMC11635009 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature