Divergent tumor immunity determined by bacteria-cancer cell engagement

# Divergent tumor immunity determined by bacteria-cancer cell engagement *Published: 2026 Mar 19* Intratumor bacteria represent an understudied yet influential component of the cancer ecosystem, critically impinging cancer progression. In PyMT breast tumors, we find intracellular bacteria, when residing in cancer cell cytosol, promote metastasis by triggering cytosolic double-stranded DNA (dsDNA) accumulation, which in turn activates the tumor intrinsic cGAS-STING-interleukin (IL)-17B pathway and redirects neutrophils toward a protumor phenotype that inhibits cytotoxic T cells. By contrast, the same strain of bacteria, when present extracellularly, induces antitumor neutrophil activity without engaging the STING pathway. Physiologically, eliminating intracellular bacteria, or therapeutically introducing extracellular bacteria components, abrogates immunosuppression and prevents postsurgical metastatic recurrence in preclinical models. Clinically, the bacteria invasion signature we have developed is associated with poor prognosis in patients with breast cancer. In summary, the spatial interplay between bacteria and host cells in metastatic niches can shape divergent tumor immunity, highlighting bacterial-host engagement as a crucial determinant of cancer immune regulation and a potential therapeutic target. DOI: 10.1016/j.cell.2025.12.044