Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway
Abstract Background The tumor immune microenvironment (TIME) and its impact on the prognoses and treatment of lung adenocarcinoma (LUAD) represent a major focus of research in this field. The present study primarily elucidates the role of RGS17 in TIME of LUAD. Methods A comprehensive array of analy...
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| Format: | Article |
| Language: | English |
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02850-3 |
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| author | Ming Lou Ji-Chun Tong Qi-Yong Wu Zheng Zhu Xiao-Liang Mao Jia-Wei Lu |
| author_facet | Ming Lou Ji-Chun Tong Qi-Yong Wu Zheng Zhu Xiao-Liang Mao Jia-Wei Lu |
| author_sort | Ming Lou |
| collection | DOAJ |
| description | Abstract Background The tumor immune microenvironment (TIME) and its impact on the prognoses and treatment of lung adenocarcinoma (LUAD) represent a major focus of research in this field. The present study primarily elucidates the role of RGS17 in TIME of LUAD. Methods A comprehensive array of analytical methods was employed to assess the gene expression levels, including RT-qPCR, Western blots assay and Immunohistochemistry. The assessment of cell apoptosis and viability was conducted through the utilization of Flow cytometry, Colony formation, or CCK-8 assays. To comprehensively evaluate glycolysis, the glucose consumption, lactate production and extracellular acidification rate (ECAR) were detected. Results RGS17 was highly expressed in LUAD patients, which predicted adverse prognosis of LUAD patients. Functionally, RGS17 promoted LUAD tumor growth by hindering the anti-tumor immune response. Specifically, knockdown of RGS17 in tumor cells was observed to result in increased CD8 + T cell infiltration into the tumors, thereby impeding LUAD tumor growth. Furthermore, tumor-secreted RGS17 impeded CD8 + T cell function by reducing IFN-γ and Granzyme B secretion, thus impeding the anti-tumor immune response. Mechanically, RGS17 impeded glycolysis in CD8 + T cells by regulating the PI3K/AKT pathway. Conclusion Tumor-secreted RGS17 impairs CD8 + T cell cytotoxicity in LUAD through impeding glycolysis mediated by PI3K/AKT pathway, thereby promoting tumor growth. |
| format | Article |
| id | doaj-art-ed60bffe98484decb25cdd920e9d56a1 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-ed60bffe98484decb25cdd920e9d56a12025-08-20T03:46:28ZengSpringerDiscover Oncology2730-60112025-07-0116111210.1007/s12672-025-02850-3Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathwayMing Lou0Ji-Chun Tong1Qi-Yong Wu2Zheng Zhu3Xiao-Liang Mao4Jia-Wei Lu5Department of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityDepartment of Thoracic Surgery, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical UniversityAbstract Background The tumor immune microenvironment (TIME) and its impact on the prognoses and treatment of lung adenocarcinoma (LUAD) represent a major focus of research in this field. The present study primarily elucidates the role of RGS17 in TIME of LUAD. Methods A comprehensive array of analytical methods was employed to assess the gene expression levels, including RT-qPCR, Western blots assay and Immunohistochemistry. The assessment of cell apoptosis and viability was conducted through the utilization of Flow cytometry, Colony formation, or CCK-8 assays. To comprehensively evaluate glycolysis, the glucose consumption, lactate production and extracellular acidification rate (ECAR) were detected. Results RGS17 was highly expressed in LUAD patients, which predicted adverse prognosis of LUAD patients. Functionally, RGS17 promoted LUAD tumor growth by hindering the anti-tumor immune response. Specifically, knockdown of RGS17 in tumor cells was observed to result in increased CD8 + T cell infiltration into the tumors, thereby impeding LUAD tumor growth. Furthermore, tumor-secreted RGS17 impeded CD8 + T cell function by reducing IFN-γ and Granzyme B secretion, thus impeding the anti-tumor immune response. Mechanically, RGS17 impeded glycolysis in CD8 + T cells by regulating the PI3K/AKT pathway. Conclusion Tumor-secreted RGS17 impairs CD8 + T cell cytotoxicity in LUAD through impeding glycolysis mediated by PI3K/AKT pathway, thereby promoting tumor growth.https://doi.org/10.1007/s12672-025-02850-3RGS17CD8 + T cellLung adenocarcinomaGlucose metabolic reprogrammingPI3K/AKT pathway |
| spellingShingle | Ming Lou Ji-Chun Tong Qi-Yong Wu Zheng Zhu Xiao-Liang Mao Jia-Wei Lu Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway Discover Oncology RGS17 CD8 + T cell Lung adenocarcinoma Glucose metabolic reprogramming PI3K/AKT pathway |
| title | Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway |
| title_full | Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway |
| title_fullStr | Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway |
| title_full_unstemmed | Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway |
| title_short | Tumor-secreted RGS17 impairs CD8 + T cell function in lung adenocarcinoma through affecting glucose metabolism mediated by PI3K/AKT pathway |
| title_sort | tumor secreted rgs17 impairs cd8 t cell function in lung adenocarcinoma through affecting glucose metabolism mediated by pi3k akt pathway |
| topic | RGS17 CD8 + T cell Lung adenocarcinoma Glucose metabolic reprogramming PI3K/AKT pathway |
| url | https://doi.org/10.1007/s12672-025-02850-3 |
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