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The tumor microenvironment (TME) presents differential selective pressure (DSP) that favors the growth of cancer cells, and monovalent therapy is often inadequate in reversing the cancer cell dominance in the TME. Dr. Mou Yun, Associate Research Fellow at the Institute of Biomedical Sciences, Academia Sinica, and his research team introduce bacteria as a foreign species to the TME and explore combinatorial treatment strategies to alter DSP for tumor eradication. The research shows that using bacteria as a therapeutic approach can modulate the tumor microenvironment against cancer cells. When combined with chemotherapy drugs or dietary interventions, the effectiveness of bacterial inhibition of cancer can be strengthened. Moreover, the research shows that an immunogenic drug (oxaliplatin), but not a non-immunogenic one (5-FU), synergizes with the bacteria to activate both the innate and adaptive immunity in the TME, resulting in complete tumor remission and a sustained anti-tumor immunological memory in mice. The combination of oxaliplatin and bacteria greatly enhances the co-stimulatory and antigen-presenting molecules on antigen-presenting cells, which in turn bridge the cytotoxic T cells for cancer-cell killing. The research findings indicate that rational combination of bacterial therapy and immunogenic chemotherapy can promote anticancer immunity against the immunosuppressive TME. This study has been published on January 20, 2024 in EMBO Molecular Medicine journal.