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Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy
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Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy
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Journal Article
Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy
2025
Overview
Immunotherapy has revolutionized cancer treatment by leveraging the patient's immune system, yet its efficacy is often hampered by the immunosuppressive tumor microenvironment (TME). Adenosine, a key player in this milieu, suppresses immune cell activity via cAMP signaling. Here, an innovative strategy to remodel the TME using a genetically engineered strain of Escherichia coli Nissle 1917 that expresses adenosine deaminase on its surface under hypoxic conditions is presented. This engineered probiotic targets tumors, converts immunosuppressive adenosine to inosine, and enhances anti‐tumor immune responses. In vivo, the engineered probiotic significantly improved immune cell infiltration and demonstrated synergistic effects with low‐dose doxorubicin in both subcutaneous and orthotopic mouse colorectal cancer model. Furthermore, the engineered probiotic modulated the TME, promoting a shift from M2‐like to M1‐like macrophages and increasing effector T cell populations. These findings highlight the potential of using engineered probiotics for metabolic modulation of the TME, offering a novel approach for enhancing cancer immunotherapy. This study presents engineered probiotics that convert immunosuppressive adenosine into inosine in tumors, alleviating immunosuppression and enhancing antitumor immunity. Demonstrating efficacy in murine ectopic and orthotopic tumor models, this approach offers a promising probiotic‐based cancer immunotherapy strategy, highlighting the potential of microbial therapeutics in oncology.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
