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      description: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. Aging-related immune alteration has been attributed to increased susceptibility to infection and cancer. Here the authors show, using both lung cancer samples and mouse models, that aged Treg cells express higher levels of an ER enzyme, SOAT2, have altered cholesterol metabolism, and induce CD8+ T cell senescence to dampen anti-tumor immunity.
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         multidisciplinary
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               name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Xiao Lu
      affiliation:
            name:Changshu No.1 People’s Hospital
            address:
               name:Changshu Hospital Affiliated to Soochow University, Changshu No.1 People’s Hospital, Changshu, China
               type:PostalAddress
            type:Organization
      name:Lang Qin
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Yu Han
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Xingwang Kuai
      affiliation:
            name:Nantong University
            address:
               name:Department of Pathology, Medical School, Nantong University, Nantong, China
               type:PostalAddress
            type:Organization
      name:Yuxing Zhang
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      name:Minjie Chu
      url:http://orcid.org/0000-0002-7533-9119
      affiliation:
            name:Nantong University
            address:
               name:Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Shuangshuang Wu
      url:http://orcid.org/0000-0002-9526-7976
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jianqing Wu
      url:http://orcid.org/0000-0003-0030-201X
      affiliation:
            name:The First Affiliated Hospital of Nanjing Medical University
            address:
               name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Centre for Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Changshu Hospital Affiliated to Soochow University, Changshu No.1 People’s Hospital, Changshu, China
      name:Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Department of Pathology, Medical School, Nantong University, Nantong, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Department of Epidemiology, School of Public Health, Nantong University, Nantong, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
      name:Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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