Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response
Summary: Sirtuin-1 (SIRT1) is a classical histone deacetylase well known for its roles in intracellular pathways such as energy metabolism, DNA damage response, and genome stability maintenance. We report that SIRT1 can be secreted into the tumor microenvironment (TME) through an unconventional prot...
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004504 |
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| author | Zhuo Wang Wendong Guo Xiaowen Zhang Yufei Wei Wanying Zhang Ning Du Chunlu Li Xuan Wu Fei Yi Tingting Zhou Xiang Dong Qiqiang Guo Hongde Xu Erli Wang Na Li Rong Cheng Ziwei Li Xiaoyu Song Yingxian Sun Xun Sun Liu Cao |
| author_facet | Zhuo Wang Wendong Guo Xiaowen Zhang Yufei Wei Wanying Zhang Ning Du Chunlu Li Xuan Wu Fei Yi Tingting Zhou Xiang Dong Qiqiang Guo Hongde Xu Erli Wang Na Li Rong Cheng Ziwei Li Xiaoyu Song Yingxian Sun Xun Sun Liu Cao |
| author_sort | Zhuo Wang |
| collection | DOAJ |
| description | Summary: Sirtuin-1 (SIRT1) is a classical histone deacetylase well known for its roles in intracellular pathways such as energy metabolism, DNA damage response, and genome stability maintenance. We report that SIRT1 can be secreted into the tumor microenvironment (TME) through an unconventional protein secretion pathway, effectively inhibiting tumor growth. However, under the stressful conditions of the TME, SIRT1 undergoes increased methylation, which impedes its secretion. Consequently, tumor-infiltrating M2 macrophages are unable to acquire sufficient SIRT1 from the TME, resulting in a significant decrease in SIRT1 levels within these cells. This SIRT1 decline leads to elevated expression of programmed cell death ligand 1 (PD-L1) on M2 macrophages, which in turn contributes to CD8+ T cell exhaustion through the programmed cell death protein 1/PD-L1 interaction pathway. These findings unveil the multifaceted roles and regulatory mechanisms of SIRT1 within the complex TME, providing deeper insights that significantly enhance our understanding of tumor immune-evasion strategies. |
| format | Article |
| id | doaj-art-e17e704476e542fa898f0a3b04cb1f81 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-e17e704476e542fa898f0a3b04cb1f812025-08-20T02:28:20ZengElsevierCell Reports2211-12472025-05-0144511567910.1016/j.celrep.2025.115679Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune responseZhuo Wang0Wendong Guo1Xiaowen Zhang2Yufei Wei3Wanying Zhang4Ning Du5Chunlu Li6Xuan Wu7Fei Yi8Tingting Zhou9Xiang Dong10Qiqiang Guo11Hongde Xu12Erli Wang13Na Li14Rong Cheng15Ziwei Li16Xiaoyu Song17Yingxian Sun18Xun Sun19Liu Cao20Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaDepartment of Immunology, Basic Medicine College, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Department of Immunology, Basic Medicine College, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, ChinaKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, China; Corresponding authorDepartment of Cardiology, First Hospital of China Medical University, Shenyang, Liaoning 110122, China; Corresponding authorDepartment of Immunology, Basic Medicine College, China Medical University, Shenyang, Liaoning 110122, China; Corresponding authorKey Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Health Sciences Institute, China Medical University, Shenyang, Liaoning 110122, China; Corresponding authorSummary: Sirtuin-1 (SIRT1) is a classical histone deacetylase well known for its roles in intracellular pathways such as energy metabolism, DNA damage response, and genome stability maintenance. We report that SIRT1 can be secreted into the tumor microenvironment (TME) through an unconventional protein secretion pathway, effectively inhibiting tumor growth. However, under the stressful conditions of the TME, SIRT1 undergoes increased methylation, which impedes its secretion. Consequently, tumor-infiltrating M2 macrophages are unable to acquire sufficient SIRT1 from the TME, resulting in a significant decrease in SIRT1 levels within these cells. This SIRT1 decline leads to elevated expression of programmed cell death ligand 1 (PD-L1) on M2 macrophages, which in turn contributes to CD8+ T cell exhaustion through the programmed cell death protein 1/PD-L1 interaction pathway. These findings unveil the multifaceted roles and regulatory mechanisms of SIRT1 within the complex TME, providing deeper insights that significantly enhance our understanding of tumor immune-evasion strategies.http://www.sciencedirect.com/science/article/pii/S2211124725004504CP: CancerCP: Immunology |
| spellingShingle | Zhuo Wang Wendong Guo Xiaowen Zhang Yufei Wei Wanying Zhang Ning Du Chunlu Li Xuan Wu Fei Yi Tingting Zhou Xiang Dong Qiqiang Guo Hongde Xu Erli Wang Na Li Rong Cheng Ziwei Li Xiaoyu Song Yingxian Sun Xun Sun Liu Cao Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response Cell Reports CP: Cancer CP: Immunology |
| title | Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response |
| title_full | Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response |
| title_fullStr | Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response |
| title_full_unstemmed | Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response |
| title_short | Tumor microenvironment-associated oxidative stress impairs SIRT1 secretion to suppress anti-tumor immune response |
| title_sort | tumor microenvironment associated oxidative stress impairs sirt1 secretion to suppress anti tumor immune response |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004504 |
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