Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells
Abstract Revealing the immunosenescence, particularly in CD4+ T cell function in lung squamous carcinoma (LUSC) assists in devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated (ROS1 MUT) and wild-type (ROS1 WT) LUSC samples from t...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03960-1 |
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| author | Peian Cai Haibo Sun Tongmeng Jiang Huawei Li Dejing Huang Xiaopei Hao Wei Wang Wenqun Xing Guanghui Liang |
| author_facet | Peian Cai Haibo Sun Tongmeng Jiang Huawei Li Dejing Huang Xiaopei Hao Wei Wang Wenqun Xing Guanghui Liang |
| author_sort | Peian Cai |
| collection | DOAJ |
| description | Abstract Revealing the immunosenescence, particularly in CD4+ T cell function in lung squamous carcinoma (LUSC) assists in devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated (ROS1 MUT) and wild-type (ROS1 WT) LUSC samples from the TCGA database. Using WGCNA, immune-related DEGs (IRGs) were screened. Prognostic signatures derived from IRGs were used to compare immune infiltration, chemotherapy sensitivity, and immune-phenotyping score (IPS) between high- and low-risk subgroups. Hub gene abundance in different cell clusters was analyzed via Sc-seq. TAGAP overexpression or silencing was employed to assess its impact on cytokines production and differentiation of CD4+ T cells, downstream c-Rel expression, and tumor progression. High-risk subgroups exhibited decreased infiltration of natural killer, follicular helper T, and CD8+ T cells, but increased plasma, CD4+ memory resting T, and macrophage M2 cells. These subgroups were more sensitive to Sunitinib and CTLA4 blockade. TAGAP expression was significantly reduced in LUSC. Overexpressing TAGAP enhanced CD4+ T cells to produce cytokines, promoted differentiation into Th1/Th17 cells, inhibited Treg conversion, and suppressed LUSC cell phenotype in vitro. TAGAP overexpression in CD4+ T cells also inhibited LUSC tumor growth and boosted immune infiltration in vivo. TAGAP’s effects on CD4+ T cells were partly reversed by c-Rel overexpression, highlighting TAGAP's role in rejuvenating CD4+ T cells and exerting anticancer effects by inhibiting c-Rel. This study elucidates the novel therapeutic potential of targeting TAGAP to modulate CD4+ T cell activity in immunotherapy for LUSC. |
| format | Article |
| id | doaj-art-e8ff78238f574af884e3477eda3c83e4 |
| institution | OA Journals |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-e8ff78238f574af884e3477eda3c83e42025-08-20T02:10:14ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174412210.1007/s00262-025-03960-1Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cellsPeian Cai0Haibo Sun1Tongmeng Jiang2Huawei Li3Dejing Huang4Xiaopei Hao5Wei Wang6Wenqun Xing7Guanghui Liang8Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalKey Laboratory of Emergency and Trauma, Ministry of Education, Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Provincial Stem Cell Research Institute, Hainan Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalDepartment of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalAbstract Revealing the immunosenescence, particularly in CD4+ T cell function in lung squamous carcinoma (LUSC) assists in devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated (ROS1 MUT) and wild-type (ROS1 WT) LUSC samples from the TCGA database. Using WGCNA, immune-related DEGs (IRGs) were screened. Prognostic signatures derived from IRGs were used to compare immune infiltration, chemotherapy sensitivity, and immune-phenotyping score (IPS) between high- and low-risk subgroups. Hub gene abundance in different cell clusters was analyzed via Sc-seq. TAGAP overexpression or silencing was employed to assess its impact on cytokines production and differentiation of CD4+ T cells, downstream c-Rel expression, and tumor progression. High-risk subgroups exhibited decreased infiltration of natural killer, follicular helper T, and CD8+ T cells, but increased plasma, CD4+ memory resting T, and macrophage M2 cells. These subgroups were more sensitive to Sunitinib and CTLA4 blockade. TAGAP expression was significantly reduced in LUSC. Overexpressing TAGAP enhanced CD4+ T cells to produce cytokines, promoted differentiation into Th1/Th17 cells, inhibited Treg conversion, and suppressed LUSC cell phenotype in vitro. TAGAP overexpression in CD4+ T cells also inhibited LUSC tumor growth and boosted immune infiltration in vivo. TAGAP’s effects on CD4+ T cells were partly reversed by c-Rel overexpression, highlighting TAGAP's role in rejuvenating CD4+ T cells and exerting anticancer effects by inhibiting c-Rel. This study elucidates the novel therapeutic potential of targeting TAGAP to modulate CD4+ T cell activity in immunotherapy for LUSC.https://doi.org/10.1007/s00262-025-03960-1T cell activating Rho GTPase-activating protein (TAGAP)CD4+ T cellImmunotherapyPrognosis signatureLung squamous cell carcinoma (LUSC) |
| spellingShingle | Peian Cai Haibo Sun Tongmeng Jiang Huawei Li Dejing Huang Xiaopei Hao Wei Wang Wenqun Xing Guanghui Liang Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells Cancer Immunology, Immunotherapy T cell activating Rho GTPase-activating protein (TAGAP) CD4+ T cell Immunotherapy Prognosis signature Lung squamous cell carcinoma (LUSC) |
| title | Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells |
| title_full | Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells |
| title_fullStr | Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells |
| title_full_unstemmed | Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells |
| title_short | Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells |
| title_sort | harnessing tagap to improve immunotherapy for lung squamous carcinoma treatment by targeting c rel in cd4 t cells |
| topic | T cell activating Rho GTPase-activating protein (TAGAP) CD4+ T cell Immunotherapy Prognosis signature Lung squamous cell carcinoma (LUSC) |
| url | https://doi.org/10.1007/s00262-025-03960-1 |
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