Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity

作     者：Nina Dumauthioz Benjamin Tschumi Mathias Wenes Bastien Marti Haiping Wang Fabien Franco Wenhui Li Isabel CLopez-Mejia Lluis Fajas Ping-Chih Ho Alena Donda Pedro Romero Lianjun Zhang Nina Dumauthioz;Benjamin Tschumi;Mathias Wenes;Bastien Marti;Haiping Wang;Fabien Franco;Wenhui Li;Isabel C.Lopez-Mejia;Lluis Fajas;Ping-Chih Ho;Alena Donda;Pedro Romero;Lianjun Zhang

作者机构：Translational Tumor Immunology GroupLudwig Cancer ResearchUniversity of LausanneEpalingesSwitzerland Department of Fundamental OncologyUniversity of LausanneEpalingesSwitzerland Department of Fundamental OncologyUniversity of LausanneEpalingesSwitzerland Ludwig Cancer Research Institute Lausanne BranchEpalingesSwitzerland Center for Systems MedicineInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College100005BeijingChina Suzhou Institute of Systems MedicineSuzhouJiangsu215123China Center for Integrative GenomicsUniversity of LausanneLausanneSwitzerland 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2021年第18卷第7期

页      面：1761-1771页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：I.C.L.-M.is supported by the Swiss National Science Foundation(Ambizione PZ00P3_168077) P.C.-H.was supported by the SNSF grant(31003A_163204),(31003A_182470) CRI-CLIP award.L.Z.and P.R.were funded in part by an SNSF grant Sinergia(CRSII3_141879) the Foundation MEDIC.ND and PR were supported in part by a SNSF Sinergia grant(CRSII3_160708) L.Zhang was also supported by the Natural Science Foundation of China(NSFC 81971466) the Chinese Academy of Medical Sciences(2016-I2M-1-005) W.L.was supported by the Natural Science Foundation of China(NSFC 31900645) 

主　　题：PGC-1α Mitochondria CD8 Memory Anti-tumor immunity 

摘      要：Memory CD8 T cells can provide long-term protection against tumors,which depends on their enhanced proliferative capacity,self-renewal and unique metabolic rewiring to sustain cellular ***,memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic *** contrast,tumor-infiltrating lymphocytes(TILs)display severe metabolic defects,which may underlie their functional ***,we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),the master regulator of mitochondrial biogenesis(MB),favors CD8 T cell central memory formation rather than resident memory ***-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide ***,CD8 T cells with enhanced PGC-1αexpression provide stronger antitumor immunity in a mouse melanoma ***,TILs overexpressing PGC-1αmaintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free ***,our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation,metabolic fitness,and antitumor immunity in vivo.