Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells
Abstract Serine arginine-rich splicing factor 1 (SRSF1) is a key oncogenic splicing factor in various cancers, promoting abnormal gene expression through post-translational regulation. Although the protumoral function of SRSF1 is well-established, the effects of inhibiting tumor-intrinsic SRSF1 on t...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02118-2 |
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| author | Gui-Qi Zhu Zheng Tang Tian-Hao Chu Biao Wang Shi-Ping Chen Chen-Yang Tao Jia-Liang Cai Rui Yang Wei-Feng Qu Yi Wang Qian-Fu Zhao Run Huang Meng-Xin Tian Yuan Fang Jun Gao Xiao-Ling Wu Jian Zhou Wei-Ren Liu Zhi Dai Ying-Hong Shi Jia Fan |
| author_facet | Gui-Qi Zhu Zheng Tang Tian-Hao Chu Biao Wang Shi-Ping Chen Chen-Yang Tao Jia-Liang Cai Rui Yang Wei-Feng Qu Yi Wang Qian-Fu Zhao Run Huang Meng-Xin Tian Yuan Fang Jun Gao Xiao-Ling Wu Jian Zhou Wei-Ren Liu Zhi Dai Ying-Hong Shi Jia Fan |
| author_sort | Gui-Qi Zhu |
| collection | DOAJ |
| description | Abstract Serine arginine-rich splicing factor 1 (SRSF1) is a key oncogenic splicing factor in various cancers, promoting abnormal gene expression through post-translational regulation. Although the protumoral function of SRSF1 is well-established, the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+ T cell-mediated antitumor immunity remain unclear. Our findings indicate that depleting SRSF1 in CD8+ T cells improve antitumor immune function, glycolytic metabolism, and the efficacy of adoptive T cell therapy. The inactivation of SRSF1 in tumor cells reduces transcription factors, including c-Jun, c-myc, and JunB, facilitating glycolytic metabolism reprogramming, which restores CD8+ T cell function and inhibits tumor growth. The small-molecule inhibitor TN2008 targets SRSF1, boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models. We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+ T cells. |
| format | Article |
| id | doaj-art-2a74ebc80c3f43f4bd9550fc562ac886 |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-2a74ebc80c3f43f4bd9550fc562ac8862025-01-26T12:54:27ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-0110111610.1038/s41392-024-02118-2Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cellsGui-Qi Zhu0Zheng Tang1Tian-Hao Chu2Biao Wang3Shi-Ping Chen4Chen-Yang Tao5Jia-Liang Cai6Rui Yang7Wei-Feng Qu8Yi Wang9Qian-Fu Zhao10Run Huang11Meng-Xin Tian12Yuan Fang13Jun Gao14Xiao-Ling Wu15Jian Zhou16Wei-Ren Liu17Zhi Dai18Ying-Hong Shi19Jia Fan20Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Radiation Oncology, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of General Surgery, Gastric cancer center, Zhongshan Hospital, Fudan UniversityDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationAbstract Serine arginine-rich splicing factor 1 (SRSF1) is a key oncogenic splicing factor in various cancers, promoting abnormal gene expression through post-translational regulation. Although the protumoral function of SRSF1 is well-established, the effects of inhibiting tumor-intrinsic SRSF1 on the tumor microenvironment and its impact on CD8+ T cell-mediated antitumor immunity remain unclear. Our findings indicate that depleting SRSF1 in CD8+ T cells improve antitumor immune function, glycolytic metabolism, and the efficacy of adoptive T cell therapy. The inactivation of SRSF1 in tumor cells reduces transcription factors, including c-Jun, c-myc, and JunB, facilitating glycolytic metabolism reprogramming, which restores CD8+ T cell function and inhibits tumor growth. The small-molecule inhibitor TN2008 targets SRSF1, boosting antitumor immune responses and improving immunotherapy effectiveness in mouse models. We therefore introduce a paradigm targeting SRSF1 that simultaneously disrupts tumor cell metabolism and enhances the antitumor immunity of CD8+ T cells.https://doi.org/10.1038/s41392-024-02118-2 |
| spellingShingle | Gui-Qi Zhu Zheng Tang Tian-Hao Chu Biao Wang Shi-Ping Chen Chen-Yang Tao Jia-Liang Cai Rui Yang Wei-Feng Qu Yi Wang Qian-Fu Zhao Run Huang Meng-Xin Tian Yuan Fang Jun Gao Xiao-Ling Wu Jian Zhou Wei-Ren Liu Zhi Dai Ying-Hong Shi Jia Fan Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells Signal Transduction and Targeted Therapy |
| title | Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells |
| title_full | Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells |
| title_fullStr | Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells |
| title_full_unstemmed | Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells |
| title_short | Targeting SRSF1 improves cancer immunotherapy by dually acting on CD8+T and tumor cells |
| title_sort | targeting srsf1 improves cancer immunotherapy by dually acting on cd8 t and tumor cells |
| url | https://doi.org/10.1038/s41392-024-02118-2 |
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