TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus
Summary: Gliomas, characterized by their robust immunosuppressive microenvironment, pose a significant challenge to the efficacy of immunotherapies. The cGas/STING signaling pathway is emerging as a promising target for cancer immunotherapy. The inhibition of ADP-ribosylation factor 1 (ARF1), a pivo...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225009575 |
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| author | Tao Cao Tong Hao Xiaoru Zhang Bo Chen Hongxuan Zhang Luocheng Shao Wenqiao He Bingnan Li Qihao Zheng Peng Ji Ke Tao |
| author_facet | Tao Cao Tong Hao Xiaoru Zhang Bo Chen Hongxuan Zhang Luocheng Shao Wenqiao He Bingnan Li Qihao Zheng Peng Ji Ke Tao |
| author_sort | Tao Cao |
| collection | DOAJ |
| description | Summary: Gliomas, characterized by their robust immunosuppressive microenvironment, pose a significant challenge to the efficacy of immunotherapies. The cGas/STING signaling pathway is emerging as a promising target for cancer immunotherapy. The inhibition of ADP-ribosylation factor 1 (ARF1), a pivotal regulator within cGas/STING signaling pathway, has been shown to enhance the activation cGas/STING. We investigated the impact of macrophage-specific ARF1 suppression on the phenotype of tumor-associated macrophages (TAMs) and the subsequent tumor specific immune response. Our findings reveal that targeted downregulation of ARF1 in TAMs substantially amplifies the immune response induced by oncolytic adenoviruses, effectively reprograms these macrophages, and bolsters anti-tumor immunity. The use of oncolytic adenoviruses armed with ARF1 knockdown elements has been demonstrated to exert a significant suppressive effect on glioma growth through the concerted action of multiple pathways and effectively elicit immune memory, thereby enhancing the survival rates of tumor bearing mice and preventing tumor recurrence. |
| format | Article |
| id | doaj-art-23bc11bfb9ca4b778a9881c8e35ea502 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-23bc11bfb9ca4b778a9881c8e35ea5022025-08-20T02:04:37ZengElsevieriScience2589-00422025-06-0128611269610.1016/j.isci.2025.112696TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirusTao Cao0Tong Hao1Xiaoru Zhang2Bo Chen3Hongxuan Zhang4Luocheng Shao5Wenqiao He6Bingnan Li7Qihao Zheng8Peng Ji9Ke Tao10Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an, Shaanxi Province 710032, ChinaDepartment of Burns and Cutaneous Surgery, Burn Center of PLA, The First Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi Province 710032, ChinaNuclear Medicine Laboratory, Tangshan People’s Hospital, Tangshan, Hebei Province 063000, ChinaSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaThe First Clinical School, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaDepartment of Wound Repair, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaDepartment of Wound Repair, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaDepartment of Wound Repair, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaThe First Clinical School, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, ChinaDepartment of Burns and Cutaneous Surgery, Burn Center of PLA, The First Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi Province 710032, China; Corresponding authorDepartment of Wound Repair, Wound Repair and Regenerative Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China; Corresponding authorSummary: Gliomas, characterized by their robust immunosuppressive microenvironment, pose a significant challenge to the efficacy of immunotherapies. The cGas/STING signaling pathway is emerging as a promising target for cancer immunotherapy. The inhibition of ADP-ribosylation factor 1 (ARF1), a pivotal regulator within cGas/STING signaling pathway, has been shown to enhance the activation cGas/STING. We investigated the impact of macrophage-specific ARF1 suppression on the phenotype of tumor-associated macrophages (TAMs) and the subsequent tumor specific immune response. Our findings reveal that targeted downregulation of ARF1 in TAMs substantially amplifies the immune response induced by oncolytic adenoviruses, effectively reprograms these macrophages, and bolsters anti-tumor immunity. The use of oncolytic adenoviruses armed with ARF1 knockdown elements has been demonstrated to exert a significant suppressive effect on glioma growth through the concerted action of multiple pathways and effectively elicit immune memory, thereby enhancing the survival rates of tumor bearing mice and preventing tumor recurrence.http://www.sciencedirect.com/science/article/pii/S2589004225009575CancerImmunologyMolecular biology |
| spellingShingle | Tao Cao Tong Hao Xiaoru Zhang Bo Chen Hongxuan Zhang Luocheng Shao Wenqiao He Bingnan Li Qihao Zheng Peng Ji Ke Tao TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus iScience Cancer Immunology Molecular biology |
| title | TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| title_full | TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| title_fullStr | TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| title_full_unstemmed | TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| title_short | TAMs-specific ARF1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| title_sort | tams specific arf1 inhibition reprograms glioma microenvironment and enhances the therapeutic effect of oncolytic adenovirus |
| topic | Cancer Immunology Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225009575 |
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