Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions and Induce Cell Cycle Arrest

Tumor infiltrating bacteria can significantly influence the tumor microenvironment and cancer progression. Spatial profiling of patient colorectal cancer (CRC) revealed that intratumoral bacteria, including Fusobacterium species, localize to tumor regions with distinct cellular composition and function. We demonstrate that these bacteria disrupt epithelial cell-to-cell contacts between neighboring cancer cells, inducing cell cycle arrest at the G0-G1 phase and transcriptional quiescence. Imaging and functional studies show this disruption can be driven by extracellular bacteria, resulting in lower cellular proliferation and increased chemoresistance, particularly to 5-fluorouracil. In a mouse model of colon adenocarcinoma, we observe tumor infiltration by Fusobacterium animalis remodels the infected tumor niche and alters spatial distribution of cancer cells. Subsequent high-resolution host-bacterial single-cell spatial transcriptomics in patient CRC tumors supported these findings. These results demonstrate the role of tumor-infiltrating Fusobacterium in modulating cancer cell behavior, proliferation, and treatment response, offering mechanistic insights into Fusobacterium-associated CRC relapse and recurrence.