Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis
Abstract Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, charact...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55164-3 |
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| author | Runping Duan Loujing Jiang Tianfu Wang Zhaohuai Li Xiaoyang Yu Yuehan Gao Renbing Jia Xianqun Fan Wenru Su |
| author_facet | Runping Duan Loujing Jiang Tianfu Wang Zhaohuai Li Xiaoyang Yu Yuehan Gao Renbing Jia Xianqun Fan Wenru Su |
| author_sort | Runping Duan |
| collection | DOAJ |
| description | Abstract Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils. Mechanistically, age-dependent downregulation of the immune trafficking receptor S1pr1 drives the expansion of γδ17. Compared to young mice, expanded γδ17 recruit tumor-promoting neutrophils with lower expression levels of CD62L and higher levels of C-kit and CXCR4. These neutrophils suppress the stemness and tumor-killing functions of CD8+ T cells in aged male mice. Accordingly, antibody-mediated depletion of γδT or neutrophils reduces tumor metastatic foci in aged animals, and the administration of the senolytic agent procyanidin C1 reverses the observed immune-mediated, tumor-promoting effects of aging. Thus, we uncover a γδ17-Neutrophil-CD8 axis that promotes aging-driven tumor metastasis in male mice and provides potential insights for managing metastatic tumors. |
| format | Article |
| id | doaj-art-b1d9b4cfad424cad8f47e68e120e5cdc |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b1d9b4cfad424cad8f47e68e120e5cdc2025-01-05T12:36:26ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-55164-3Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axisRunping Duan0Loujing Jiang1Tianfu Wang2Zhaohuai Li3Xiaoyang Yu4Yuehan Gao5Renbing Jia6Xianqun Fan7Wenru Su8State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou University of Chinese MedicineState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceAbstract Aging is associated with increased tumor metastasis and poor prognosis. However, how an aging immune system contributes to the process is unclear. Here, single-cell RNA sequencing reveals that in male mice, aging shifts the lung immune microenvironment towards a premetastatic niche, characterized by an increased proportion of IL-17-expressing γδT (γδ17) and neutrophils. Mechanistically, age-dependent downregulation of the immune trafficking receptor S1pr1 drives the expansion of γδ17. Compared to young mice, expanded γδ17 recruit tumor-promoting neutrophils with lower expression levels of CD62L and higher levels of C-kit and CXCR4. These neutrophils suppress the stemness and tumor-killing functions of CD8+ T cells in aged male mice. Accordingly, antibody-mediated depletion of γδT or neutrophils reduces tumor metastatic foci in aged animals, and the administration of the senolytic agent procyanidin C1 reverses the observed immune-mediated, tumor-promoting effects of aging. Thus, we uncover a γδ17-Neutrophil-CD8 axis that promotes aging-driven tumor metastasis in male mice and provides potential insights for managing metastatic tumors.https://doi.org/10.1038/s41467-024-55164-3 |
| spellingShingle | Runping Duan Loujing Jiang Tianfu Wang Zhaohuai Li Xiaoyang Yu Yuehan Gao Renbing Jia Xianqun Fan Wenru Su Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis Nature Communications |
| title | Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis |
| title_full | Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis |
| title_fullStr | Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis |
| title_full_unstemmed | Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis |
| title_short | Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis |
| title_sort | aging induced immune microenvironment remodeling fosters melanoma in male mice via γδ17 neutrophil cd8 axis |
| url | https://doi.org/10.1038/s41467-024-55164-3 |
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