Intratumoral E.coli T30 in breast cancer: impact on CHI3L1 and PD-L1 expression and its immunomodulatory effects

Breast cancer is a multifaceted disease influenced by a variety of factors, including the tumor microenvironment and the host microbiota. Emerging evidence has highlighted the presence of intratumoral bacteria in different cancer types, with potential implications for tumor progression and immune modulation. In this study, we characterized an intratumoral Escherichia coli strain, E. coli T30, previously isolated from the 4T1 murine breast cancer model in our laboratory. Whole-genome sequencing revealed a high similarity between E. coli T30 and another E. coli strain (C17) with a pro-tumorigenic activity, capable of disrupting the gut vascular barrier and promoting metastasis. Our in vitro experiments demonstrated that E. coli T30 infection induces the overexpression of Chitinase-3-like protein 1 (CHI3L1) and Programmed Death-Ligand 1 (PD-L1) in 4T1 cells, two key immunomodulatory proteins involved in tumor immune escape. In vivo, E. coli T30-infected tumors exhibited increased growth rates, altered immune cell populations, and an immunosuppressive microenvironment characterized by elevated CHI3L1 and PD-L1 expression. Furthermore, our findings indicate that E. coli T30 enhances tumor sensitivity to anti-PD-L1 therapy, suggesting a potential therapeutic window for immune checkpoint inhibitors in tumors harboring this bacterium. Finally, the detection of E. coli T30 in human triple-negative and HER2+ breast cancer samples underscore its clinical relevance, with potential prognostic and therapeutic implications. Collectively, our findings provide new insights into the role of intratumoral bacteria in breast cancer progression and immune modulation, paving the way for microbiome-targeted therapeutic strategies.