Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity
IntroductionLung cancer is the leading cause of cancer-related death worldwide, and its morbidity and mortality are increasing. Although low-dose CT lung cancer screening has been shown to reduce lung cancer mortality, its adoption rate is limited and the pace of its promotion is slow, highlighting...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500417/full |
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| author | Zhe Zhang Yimeng Xia Yimeng Xia Zhihong Wang Yaxing Sun Dan Pu Yijia He Ruixian Liu Yanru Zhang Yan Liu Junzhi Yu Shiyang Ning Baisui Feng Yaohe Wang Na Wang |
| author_facet | Zhe Zhang Yimeng Xia Yimeng Xia Zhihong Wang Yaxing Sun Dan Pu Yijia He Ruixian Liu Yanru Zhang Yan Liu Junzhi Yu Shiyang Ning Baisui Feng Yaohe Wang Na Wang |
| author_sort | Zhe Zhang |
| collection | DOAJ |
| description | IntroductionLung cancer is the leading cause of cancer-related death worldwide, and its morbidity and mortality are increasing. Although low-dose CT lung cancer screening has been shown to reduce lung cancer mortality, its adoption rate is limited and the pace of its promotion is slow, highlighting the urgent need for more effective prevention measures. Prophylactic vaccines play a crucial role in cancer prevention. Our previous studies indicated that mice immunized with a prophylactic vaccine based on lung cancer cell lines KPL 160302S, derived from early-stage murine lung cancer tissues, exhibited a significantly extended survival period, with a strong anti-tumor immune response. While the vaccine based on KPL 160424S, derived from advanced-stage murine lung cancer tissues, failed to extend survival time and demonstrated limited capacity to stimulate anti-tumor immunity. MethodsTo investigate the fundamental reason for the difference between KPL 160302S and KPL 160424S vaccines, we employed bioinformatics methods and immune related experiments to explore the effects and mechanisms of the screened neoantigens. ResultsOur findings demonstrated that immunization with the Ddx21 mutant peptide (Ddx21MT), unique to KPL 160302S, could significantly increase the proportion of central memory T cells (TCM) in mice and activate anti-tumor immunity. DiscussionThese results suggest that the Ddx21MT is a highly effective neoantigen that can activate anti-tumor immunity, which can serve as an important component in developing a lung cancer vaccine and is expected to be used in combination with other immunotherapy approaches. |
| format | Article |
| id | doaj-art-b0efaeb1dbc947c5a0d43799c2a8c319 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b0efaeb1dbc947c5a0d43799c2a8c3192025-02-06T07:09:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15004171500417Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunityZhe Zhang0Yimeng Xia1Yimeng Xia2Zhihong Wang3Yaxing Sun4Dan Pu5Yijia He6Ruixian Liu7Yanru Zhang8Yan Liu9Junzhi Yu10Shiyang Ning11Baisui Feng12Yaohe Wang13Na Wang14Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCentre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United KingdomDepartment of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaIntroductionLung cancer is the leading cause of cancer-related death worldwide, and its morbidity and mortality are increasing. Although low-dose CT lung cancer screening has been shown to reduce lung cancer mortality, its adoption rate is limited and the pace of its promotion is slow, highlighting the urgent need for more effective prevention measures. Prophylactic vaccines play a crucial role in cancer prevention. Our previous studies indicated that mice immunized with a prophylactic vaccine based on lung cancer cell lines KPL 160302S, derived from early-stage murine lung cancer tissues, exhibited a significantly extended survival period, with a strong anti-tumor immune response. While the vaccine based on KPL 160424S, derived from advanced-stage murine lung cancer tissues, failed to extend survival time and demonstrated limited capacity to stimulate anti-tumor immunity. MethodsTo investigate the fundamental reason for the difference between KPL 160302S and KPL 160424S vaccines, we employed bioinformatics methods and immune related experiments to explore the effects and mechanisms of the screened neoantigens. ResultsOur findings demonstrated that immunization with the Ddx21 mutant peptide (Ddx21MT), unique to KPL 160302S, could significantly increase the proportion of central memory T cells (TCM) in mice and activate anti-tumor immunity. DiscussionThese results suggest that the Ddx21MT is a highly effective neoantigen that can activate anti-tumor immunity, which can serve as an important component in developing a lung cancer vaccine and is expected to be used in combination with other immunotherapy approaches.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500417/fulllung cancerprophylactic vaccineneoantigenDdx21central memory T cells |
| spellingShingle | Zhe Zhang Yimeng Xia Yimeng Xia Zhihong Wang Yaxing Sun Dan Pu Yijia He Ruixian Liu Yanru Zhang Yan Liu Junzhi Yu Shiyang Ning Baisui Feng Yaohe Wang Na Wang Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity Frontiers in Immunology lung cancer prophylactic vaccine neoantigen Ddx21 central memory T cells |
| title | Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity |
| title_full | Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity |
| title_fullStr | Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity |
| title_full_unstemmed | Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity |
| title_short | Ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long-term anti-tumor immunity |
| title_sort | ddx21 mutant peptide is an effective neoantigen in prophylactic lung cancer vaccines and activates long term anti tumor immunity |
| topic | lung cancer prophylactic vaccine neoantigen Ddx21 central memory T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1500417/full |
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