Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity
Abstract Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOA...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56002-w |
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| _version_ | 1832594566055723008 |
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| author | Mingjiong Zhang Jiahua Cui Haoyan Chen Yifan Cheng Qiaoyu Chen Feng Zong Xiao Lu Lang Qin Yu Han Xingwang Kuai Yuxing Zhang Minjie Chu Shuangshuang Wu Jianqing Wu |
| author_facet | Mingjiong Zhang Jiahua Cui Haoyan Chen Yifan Cheng Qiaoyu Chen Feng Zong Xiao Lu Lang Qin Yu Han Xingwang Kuai Yuxing Zhang Minjie Chu Shuangshuang Wu Jianqing Wu |
| author_sort | Mingjiong Zhang |
| collection | DOAJ |
| description | Abstract Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOAT2), is overexpressed in regulatory T (Treg) cells from elderly patients with lung squamous cell carcinoma (LSCC), while radiomics analysis of LSCC patients associates increased SOAT2 expression with reduced immune infiltration and poor prognosis. Mechanically, ex vivo human and mouse Treg cell data and in vivo mouse tumor models suggest that SOAT2 overexpression in Treg cells promotes cholesterol metabolism by activating the SREBP2-HMGCR-GGPP pathway, leading to enhanced Treg suppresser functions but reduced CD8+ T cell proliferation, migration, homeostasis and anti-tumor immunity. Our study thus identifies a potential mechanism responsible for altered Treg function in the context of immune aging, and also implicates SOAT2 as a potential target for tumor immunotherapy. |
| format | Article |
| id | doaj-art-ae2b3f4cad86422f92601f875f39ab40 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ae2b3f4cad86422f92601f875f39ab402025-01-19T12:31:25ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-025-56002-wIncreased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunityMingjiong Zhang0Jiahua Cui1Haoyan Chen2Yifan Cheng3Qiaoyu Chen4Feng Zong5Xiao Lu6Lang Qin7Yu Han8Xingwang Kuai9Yuxing Zhang10Minjie Chu11Shuangshuang Wu12Jianqing Wu13Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Epidemiology, School of Public Health, Nantong UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityCentre for Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of MedicineJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityChangshu Hospital Affiliated to Soochow University, Changshu No.1 People’s HospitalDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Pathology, Medical School, Nantong UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Epidemiology, School of Public Health, Nantong UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOAT2), is overexpressed in regulatory T (Treg) cells from elderly patients with lung squamous cell carcinoma (LSCC), while radiomics analysis of LSCC patients associates increased SOAT2 expression with reduced immune infiltration and poor prognosis. Mechanically, ex vivo human and mouse Treg cell data and in vivo mouse tumor models suggest that SOAT2 overexpression in Treg cells promotes cholesterol metabolism by activating the SREBP2-HMGCR-GGPP pathway, leading to enhanced Treg suppresser functions but reduced CD8+ T cell proliferation, migration, homeostasis and anti-tumor immunity. Our study thus identifies a potential mechanism responsible for altered Treg function in the context of immune aging, and also implicates SOAT2 as a potential target for tumor immunotherapy.https://doi.org/10.1038/s41467-025-56002-w |
| spellingShingle | Mingjiong Zhang Jiahua Cui Haoyan Chen Yifan Cheng Qiaoyu Chen Feng Zong Xiao Lu Lang Qin Yu Han Xingwang Kuai Yuxing Zhang Minjie Chu Shuangshuang Wu Jianqing Wu Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity Nature Communications |
| title | Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity |
| title_full | Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity |
| title_fullStr | Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity |
| title_full_unstemmed | Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity |
| title_short | Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity |
| title_sort | increased soat2 expression in aged regulatory t cells is associated with altered cholesterol metabolism and reduced anti tumor immunity |
| url | https://doi.org/10.1038/s41467-025-56002-w |
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