4-1BB signaling activates glucose and fatty acid metabolism to enhance CD8^(+) T cell proliferation
作者机构：Cancer Immunology BranchDivision of Cancer BiologyNational Cancer CenterGoyangGyeonggi 10408Korea Department of Internal MedicineYonsei University College of MedicineSeoul 120-752Korea Immune Cell Production UnitProgram for Immunotherapeutic ResearchNational Cancer CenterGyeonggi 10408Korea EutilexCatholic University School of MedicineSeoul 06591Korea Department of MedicineTulane University Health Sciences CenterNew OrleansLA 70112USA
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2017年第14卷第9期
页 面：748-757页
核心收录：
学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：funded by grants from the National Cancer Center of Korea(NCC-1310430) the National Research Foundation of Korea(NRF-2005-0093837,NRF-2013R1A1A2008703) the Korea Drug Development Fund(KDDF-201408-11) the Ministry of Trade,Industry and Energy of Korea(GLOBAL R&D PROJECT,N0000901)
主 题：AMPK CD8^(+)T cells 4-1BB(CD137) LKB1 metabolism
摘 要：4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T *** these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid *** found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and *** with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid ***-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty *** also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB *** increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,*** conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.
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