Stenotrophomonas suppresses MHC-II+ macrophage to promote gastrointestinal tumor progression via inducing endoplasmic reticulum associated degradation of STING

While numerous studies have reported that intratumor bacteria modulate tumor biological characteristics and therapeutic outcomes, the role of intracellular bacteria in gastrointestinal tumor (GIT) progression remains largely unexplored. Here we identified that Stenotrophomonas (SP) is associated with tumor progression and poor prognosis in GIT, primarily through bioinformatics prediction and patient sample validation. Using various mouse models, we found that intracellular SP promotes GIT progression by decreasing IFN-beta secretion and inhibiting MHC-II+ macrophages, thereby impairing the activity of effector CD8 T cells. Mechanistically, SP entry into tumor cells induces endoplasmic reticulum stress, degrades STING protein, and downregulates the type I IFN pathway response. Additionally, SP contributes to resistance to chemotherapy and immunotherapy in GIT, which can be reversed by levofloxacin. Our findings indicate that intracellular SP within tumor cells plays an important role in promoting GIT progression, drug therapy resistance, and poor prognosis, and could serve as a potential target to improve outcomes for patients with GIT.