CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages
Abstract CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor‐associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA‐CpG@ID...
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412881 |
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| author | Jiaqiang Xiong Juyuan Huang Hanxiao Xu Qiuji Wu Jiahui Zhao Yurou Chen Guanlan Fan Haotong Guan Rourou Xiao Zhaojin He Siqi Wu Wenliang Ouyang Shixuan Wang Lu Zhang Peng Xia Wei Zhang Meng Wu |
| author_facet | Jiaqiang Xiong Juyuan Huang Hanxiao Xu Qiuji Wu Jiahui Zhao Yurou Chen Guanlan Fan Haotong Guan Rourou Xiao Zhaojin He Siqi Wu Wenliang Ouyang Shixuan Wang Lu Zhang Peng Xia Wei Zhang Meng Wu |
| author_sort | Jiaqiang Xiong |
| collection | DOAJ |
| description | Abstract CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor‐associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA‐CpG@ID8‐M) is engineered by encapsulating CpG within PLGA using ID8 ovarian cancer cell membranes (ID8‐M). This nanovaccine demonstrates remarkable efficacy in reprogramming TAMs in ovarian cancer and significantly extends survival in ID8‐bearing mice. Notably, these findings indicate that the nanovaccine can also mitigate chemotherapy‐induced immunosuppression by increasing the proportion of M1‐like TAMs and reducing the expression of CD47 on tumor cells, thereby achieving a synergistic effect in tumor immunotherapy. Mechanistically, through transcriptome sequencing (RNA‐seq), single‐cell RNA sequencing (scRNA‐seq), and mass spectrometry‐based proteomics, it is elucidated that the nanovaccine enhances the expression of Gbp2 and promotes the recruitment of Pin1, which activates the NFκB signaling pathway, leading to the M1 polarization of TAMs. Furthermore, macrophages with elevated Gbp2 expression significantly inhibit tumor growth in both ID8 ovarian cancer and 4T1 breast cancer models. Conversely, targeting Gbp2 diminishes the antitumor efficacy of the nanovaccine in vivo. This study offers an innovative approach to immunotherapy and elucidates a novel mechanism (Gbp2‐Pin1‐NFκB pathway) for remodeling TAMs. |
| format | Article |
| id | doaj-art-9285cb4ef84e41139fa048e9f8bacaf2 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9285cb4ef84e41139fa048e9f8bacaf22025-08-20T02:17:28ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202412881CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated MacrophagesJiaqiang Xiong0Juyuan Huang1Hanxiao Xu2Qiuji Wu3Jiahui Zhao4Yurou Chen5Guanlan Fan6Haotong Guan7Rourou Xiao8Zhaojin He9Siqi Wu10Wenliang Ouyang11Shixuan Wang12Lu Zhang13Peng Xia14Wei Zhang15Meng Wu16Department of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Gastrointestinal Oncology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Radiation and Medical Oncology Hubei Key Laboratory of Tumor Biological Behavior Hubei Provincial Clinical Research Center for Cancer Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaThe Second Clinical College of Wuhan University Wuhan 430071 ChinaThe Second Clinical College of Wuhan University Wuhan 430071 ChinaThe Second Clinical College of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430032 ChinaHubei Key Laboratory of Radiation Chemistry and Functional Materials School of Nuclear Technology and Chemistry & Biology Hubei University of Science and Technology Xianning 437100 ChinaDepartment of Hepatobiliary & Pancreatic Surgery Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Wuhan 430071 ChinaDepartment of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430032 ChinaAbstract CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor‐associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA‐CpG@ID8‐M) is engineered by encapsulating CpG within PLGA using ID8 ovarian cancer cell membranes (ID8‐M). This nanovaccine demonstrates remarkable efficacy in reprogramming TAMs in ovarian cancer and significantly extends survival in ID8‐bearing mice. Notably, these findings indicate that the nanovaccine can also mitigate chemotherapy‐induced immunosuppression by increasing the proportion of M1‐like TAMs and reducing the expression of CD47 on tumor cells, thereby achieving a synergistic effect in tumor immunotherapy. Mechanistically, through transcriptome sequencing (RNA‐seq), single‐cell RNA sequencing (scRNA‐seq), and mass spectrometry‐based proteomics, it is elucidated that the nanovaccine enhances the expression of Gbp2 and promotes the recruitment of Pin1, which activates the NFκB signaling pathway, leading to the M1 polarization of TAMs. Furthermore, macrophages with elevated Gbp2 expression significantly inhibit tumor growth in both ID8 ovarian cancer and 4T1 breast cancer models. Conversely, targeting Gbp2 diminishes the antitumor efficacy of the nanovaccine in vivo. This study offers an innovative approach to immunotherapy and elucidates a novel mechanism (Gbp2‐Pin1‐NFκB pathway) for remodeling TAMs.https://doi.org/10.1002/advs.202412881Gbp2immunotherapynanovaccineovarian cancerTAMs |
| spellingShingle | Jiaqiang Xiong Juyuan Huang Hanxiao Xu Qiuji Wu Jiahui Zhao Yurou Chen Guanlan Fan Haotong Guan Rourou Xiao Zhaojin He Siqi Wu Wenliang Ouyang Shixuan Wang Lu Zhang Peng Xia Wei Zhang Meng Wu CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages Advanced Science Gbp2 immunotherapy nanovaccine ovarian cancer TAMs |
| title | CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages |
| title_full | CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages |
| title_fullStr | CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages |
| title_full_unstemmed | CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages |
| title_short | CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages |
| title_sort | cpg based nanovaccines enhance ovarian cancer immune response by gbp2 mediated remodeling of tumor associated macrophages |
| topic | Gbp2 immunotherapy nanovaccine ovarian cancer TAMs |
| url | https://doi.org/10.1002/advs.202412881 |
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