Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis
Background Immunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.Methods To address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype mac...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/5/e006516.full |
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| author | Yan Liu Junjie Liu Qin Wang Kun Zhang Chunyan Zhu Duo Wang Guanhua Qiu Xiaoqi Zhu Chao Fang |
| author_facet | Yan Liu Junjie Liu Qin Wang Kun Zhang Chunyan Zhu Duo Wang Guanhua Qiu Xiaoqi Zhu Chao Fang |
| author_sort | Yan Liu |
| collection | DOAJ |
| description | Background Immunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.Methods To address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype macrophages. The delivered RSL3 that serves as a common ferroptosis inducer can reduce the levels of ferroptosis hallmarkers (eg, glutathione and glutathione peroxidase 4), break the redox homeostasis to magnify oxidative stress accumulation, promote the expression of ferroptosis-related proteins, and induce robust ferroptosis of tumor cells, accompanied with which systematic immune response activation can bbe realized. M1 macrophage-derived exosomes can inherit more functions and genetic substances than nanovesicles since nanovesicles inevitably suffer from substance and function loss caused by extrusion-arised structural damage.Results Inspired by it, spontaneous homing to tumor and M2-like macrophage polarization into M1-like ones are attained, which not only significantly magnify oxidative stress but also mitigate ITM including M2-like macrophage polarization and regulatory T cell decrease, and regulate death pathways.Conclusions All these actions accomplish a synergistic antitumor enhancement against tumor progression, thus paving a general route to mitigate ITM, activate immune responses, and magnify ferroptosis. |
| format | Article |
| id | doaj-art-cb428313e24c43e0a0d131da306a68ea |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-cb428313e24c43e0a0d131da306a68ea2025-02-04T12:10:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-05-0111510.1136/jitc-2022-006516Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosisYan Liu0Junjie Liu1Qin Wang2Kun Zhang3Chunyan Zhu4Duo Wang5Guanhua Qiu6Xiaoqi Zhu7Chao Fang8Department of Medical Ultrasound, Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China1 Henan Human Sperm Bank, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China6 Department of pharmacy, Guli Community Health Service Center, Nanjing, Jiangsu, ChinaCentral Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Tongji University, Shanghai, ChinaCentral Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Tongji University, Shanghai, ChinaDepartment of Medical Ultrasound, Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, ChinaDepartment of Medical Ultrasound, Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, ChinaKey Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China2Wuhan, ChinaBackground Immunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.Methods To address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype macrophages. The delivered RSL3 that serves as a common ferroptosis inducer can reduce the levels of ferroptosis hallmarkers (eg, glutathione and glutathione peroxidase 4), break the redox homeostasis to magnify oxidative stress accumulation, promote the expression of ferroptosis-related proteins, and induce robust ferroptosis of tumor cells, accompanied with which systematic immune response activation can bbe realized. M1 macrophage-derived exosomes can inherit more functions and genetic substances than nanovesicles since nanovesicles inevitably suffer from substance and function loss caused by extrusion-arised structural damage.Results Inspired by it, spontaneous homing to tumor and M2-like macrophage polarization into M1-like ones are attained, which not only significantly magnify oxidative stress but also mitigate ITM including M2-like macrophage polarization and regulatory T cell decrease, and regulate death pathways.Conclusions All these actions accomplish a synergistic antitumor enhancement against tumor progression, thus paving a general route to mitigate ITM, activate immune responses, and magnify ferroptosis.https://jitc.bmj.com/content/11/5/e006516.full |
| spellingShingle | Yan Liu Junjie Liu Qin Wang Kun Zhang Chunyan Zhu Duo Wang Guanhua Qiu Xiaoqi Zhu Chao Fang Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis Journal for ImmunoTherapy of Cancer |
| title | Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis |
| title_full | Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis |
| title_fullStr | Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis |
| title_full_unstemmed | Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis |
| title_short | Macrophage-inherited exosome excise tumor immunosuppression to expedite immune-activated ferroptosis |
| title_sort | macrophage inherited exosome excise tumor immunosuppression to expedite immune activated ferroptosis |
| url | https://jitc.bmj.com/content/11/5/e006516.full |
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