Stenotrophomonas promotes gastrointestinal tumor progression via STING degradation in tumour cells and mitigated immune response

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 show, through bioinformatics prediction and consecutive patient sample validation, that Stenotrophomonas is associated with tumor progression and poor prognosis in GIT. Using various murine tumor models, we find that intracellular Stenotrophomonas promotes GIT progression by decreasing IFNβ secretion and inhibiting MHC-II+ macrophages, thereby impairing the activity of effector CD8+ T cells. Mechanistically, Stenotrophomonas entry into tumor cells induces endoplasmic reticulum stress, degrades STING protein, and downregulates the type I IFN pathway response. Additionally, Stenotrophomonas contributes to resistance to immunotherapy in GIT, which can be reversed by levofloxacin. Our findings indicate that intracellular Stenotrophomonas within tumor cells plays an important role in promoting GIT progression and poor prognosis and could serve as a potential target to improve outcomes for patients with GIT. Bacteria can infect tumour cells which may affect the biological characteristics of the tumour or even the therapeutic outcome. Here authors show that Stenotrophomonas, upon entering tumour cells, trigger endoplasmic reticulum stress, leading to STING degradation and inhibition of MHC-II+ macrophages, which ultimately cause tumour progression and immunotherapy resistance.