Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy
Abstract 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 in...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202411813 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849700976467902464 |
|---|---|
| author | Jinhui Wang Jing Wang Zhijie Yu Hongyu Wen Chensi Zhao Jiayong Zhong Chuanle Xiao Yingqiu Li Jianqiao Xu Jinquan Wang Zong‐Wan Mao Wei Xia |
| author_facet | Jinhui Wang Jing Wang Zhijie Yu Hongyu Wen Chensi Zhao Jiayong Zhong Chuanle Xiao Yingqiu Li Jianqiao Xu Jinquan Wang Zong‐Wan Mao Wei Xia |
| author_sort | Jinhui Wang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-c6bacb531d9e4f218ab20af62fbb13f9 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-c6bacb531d9e4f218ab20af62fbb13f92025-08-20T03:18:05ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202411813Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐ImmunotherapyJinhui Wang0Jing Wang1Zhijie Yu2Hongyu Wen3Chensi Zhao4Jiayong Zhong5Chuanle Xiao6Yingqiu Li7Jianqiao Xu8Jinquan Wang9Zong‐Wan Mao10Wei Xia11MOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaGuangdong Key Laboratory of Advanced Drug Delivery School of Bioscience and Biopharmaceutics Guangdong Pharmaceutical University Guangzhou 510006 ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaState Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou 510006 ChinaState Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Sun Yat‐sen University Guangzhou 510060 ChinaState Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Sun Yat‐sen University Guangzhou 510060 ChinaState Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou 510006 ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaGuangdong Key Laboratory of Advanced Drug Delivery School of Bioscience and Biopharmaceutics Guangdong Pharmaceutical University Guangzhou 510006 ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaMOE Key Laboratory of Bioinorganic and Synthetic Chemistry IGCME School of Chemistry Sun Yat‐Sen University Guangzhou 510006 ChinaAbstract 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.https://doi.org/10.1002/advs.202411813adenosine deaminasechemo‐immunotherapyengineered probioticmetabolic modulationtumor microenvironment |
| spellingShingle | Jinhui Wang Jing Wang Zhijie Yu Hongyu Wen Chensi Zhao Jiayong Zhong Chuanle Xiao Yingqiu Li Jianqiao Xu Jinquan Wang Zong‐Wan Mao Wei Xia Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy Advanced Science adenosine deaminase chemo‐immunotherapy engineered probiotic metabolic modulation tumor microenvironment |
| title | Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy |
| title_full | Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy |
| title_fullStr | Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy |
| title_full_unstemmed | Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy |
| title_short | Targeting the Adenosine‐Mediated Metabolic Immune Checkpoint with Engineered Probiotic for Enhanced Chemo‐Immunotherapy |
| title_sort | targeting the adenosine mediated metabolic immune checkpoint with engineered probiotic for enhanced chemo immunotherapy |
| topic | adenosine deaminase chemo‐immunotherapy engineered probiotic metabolic modulation tumor microenvironment |
| url | https://doi.org/10.1002/advs.202411813 |
| work_keys_str_mv | AT jinhuiwang targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT jingwang targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT zhijieyu targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT hongyuwen targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT chensizhao targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT jiayongzhong targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT chuanlexiao targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT yingqiuli targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT jianqiaoxu targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT jinquanwang targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT zongwanmao targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy AT weixia targetingtheadenosinemediatedmetabolicimmunecheckpointwithengineeredprobioticforenhancedchemoimmunotherapy |