Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulati...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2322173 |
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| author | Wei Wei Linqing Tian Xiaoyan Zheng Lei Zhong Yuan Chen Hui Dong Guibing Zhang Shibing Wang Xiangmin Tong |
| author_facet | Wei Wei Linqing Tian Xiaoyan Zheng Lei Zhong Yuan Chen Hui Dong Guibing Zhang Shibing Wang Xiangmin Tong |
| author_sort | Wei Wei |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulation of tumor microenvironment (TME) and cause-specific T-cell responses. To boost tumor sensitivity to ICB therapy, this study aimed to investigate how glutathione peroxide 4 (GPX4)-loaded OVs affect CD8+ T cells and repair the immunosuppressive environment. Here, we successfully constructed a novel recombinant oncolytic vaccinia virus (OVV) encoding the mouse GPX4 gene. We found the OVV-GPX4 effectively replicated in tumor cells and prompted the expression of GPX4 in T cells. Our research indicated that OVV-GPX4 could reshape the TME, rectify the depletion of CD8+T cells, and enhance the antitumor effects of ICB therapy. |
| format | Article |
| id | doaj-art-2f9bb22f793f46ba9af769c26eb24f3d |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-2f9bb22f793f46ba9af769c26eb24f3d2024-12-03T13:49:35ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2322173Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinomaWei Wei0Linqing Tian1Xiaoyan Zheng2Lei Zhong3Yuan Chen4Hui Dong5Guibing Zhang6Shibing Wang7Xiangmin Tong8Zhejiang Provincial People’s Hospital Affiliated People’s Hospital, Hangzhou Medical College, Postgraduate Training Base of Jinzhou Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaDepartment of Clinical Medicine, Bengbu Medical College, Bengbu, ChinaDepartment of Laboratory Medicine, Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Laboratory Medicine, Tongxiang Traditional Chinese Medicine Hospital, Tongxiang, Zhejiang, ChinaDepartment of Pathology, Zhejiang Provincial People’s Hospital Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaDepartment of Stomatology, Punan Hospital of Pudong New District, Shanghai, ChinaDepartment of Hematology, Hangzhou Fuyang First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaKey Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Clinical Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaPancreatic ductal adenocarcinoma (PDAC) is currently difficult to treat, even when therapies are combined with immune checkpoint blockade (ICB). A novel strategy for immunotherapy would be to maximize the therapeutic potential of oncolytic viruses (OVs), which have been proven to engage the regulation of tumor microenvironment (TME) and cause-specific T-cell responses. To boost tumor sensitivity to ICB therapy, this study aimed to investigate how glutathione peroxide 4 (GPX4)-loaded OVs affect CD8+ T cells and repair the immunosuppressive environment. Here, we successfully constructed a novel recombinant oncolytic vaccinia virus (OVV) encoding the mouse GPX4 gene. We found the OVV-GPX4 effectively replicated in tumor cells and prompted the expression of GPX4 in T cells. Our research indicated that OVV-GPX4 could reshape the TME, rectify the depletion of CD8+T cells, and enhance the antitumor effects of ICB therapy.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2322173Glutathione peroxide 4oncolytic vaccinia viruspancreatic ductal adenocarcinomatumor microenvironment |
| spellingShingle | Wei Wei Linqing Tian Xiaoyan Zheng Lei Zhong Yuan Chen Hui Dong Guibing Zhang Shibing Wang Xiangmin Tong Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma OncoImmunology Glutathione peroxide 4 oncolytic vaccinia virus pancreatic ductal adenocarcinoma tumor microenvironment |
| title | Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma |
| title_full | Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma |
| title_fullStr | Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma |
| title_short | Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8+T cell function and its impact against pancreatic ductal adenocarcinoma |
| title_sort | expression of gpx4 by oncolytic vaccinia virus can significantly enhance cd8 t cell function and its impact against pancreatic ductal adenocarcinoma |
| topic | Glutathione peroxide 4 oncolytic vaccinia virus pancreatic ductal adenocarcinoma tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2322173 |
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