Glucose metabolism controls humanγδ-cell-mediated tumor immunosurveillance in diabetes
作者机构：Department of Pediatrics and Adolescent MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARPR China The First Affliated HospitalFaculty of Medical ScienceJinan UniversityGuangzhou 510632 GuangdongPR China Zhuhai Precision Medical CenterZhuhai People's Hospital(Zhuhai Hospital Affliated with Jinan University)Jinan UniversityZhuhai 519000 GuangdongPR China The Biomedical Translational Research InstituteJinan UniversityGuangzhou 510632 GuangdongPR China GuangDong 999 Brain HospitalGuangzhou CityGuangdong ProvincePR China Department of EndocrinologyGuangzhou First People's HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510180PR China Computational and Systems Biology Interdepartmental ProgramUniversity of CaliforniaLos AngelesLos AngelesCA 90095USA
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2022年第19卷第8期
页 面：944-956页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：Seed Funding for Strategic Interdisciplinary Research Scheme,University of Hong Kong,and the General Research Fund,Research Grants Council of Hong Kong(17122222,17122519,17126317),Hong Kong SAR,China This work was also partly supported by the National Natural Science Foundation of China(32000616),China
主 题：γδT cells Glucose metabolism Tumor surveillance Lactate AMPK T2DM
摘 要：Patients with type 2 diabetes mellitus(T2DM)have an increased risk of *** effect of glucose metabolism onγδT cells and their impact on tumor surveillance remain ***,we showed that high glucose induced Warburg effect type of bioenergetic profle in Vy9vδ2 T cells,leading to excessive lactate accumulation,which further inhibited lytic granule secretion by impairing the traffcking of cytolytic machinery to the Vy9vδ2 T-cell-tumor synapse by suppressing AMPK activation and resulted in the loss of antitumor activity in vitro,in vivo and in ***,activating the AMPK pathway through glucose control or metformin treatment reversed the metabolic abnormalities and restored the antitumor activity of Vy9vδ2 T *** results suggest that the impaired antitumor activity of Vy9vδ2 T cells induced by dysregulated glucose metabolism may contribute to the increased cancer risk in T2DM patients and that metabolic reprogramming by targeting the AMPK pathway with metformin may improve tumor immunosurveillance.
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