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

查看全文 作　　者：Nina [1,2]Dumauthioz;Benjamin [1,2]Tschumi;Mathias [1,2]Wenes;Bastien [1,2]Marti;Haiping [2,3]Wang;Fabien [2,3]Franco;Wenhui [4,5]Li;Isabel CLopez-[6]Mejia;Lluis [6]Fajas;Ping-Chih [2,3]Ho;Alena [1,2]Donda;Pedro [1,2]Romero;Lianjun [1,2,4,5]Zhang

机构地区：[1]Translational Tumor Immunology Group,Ludwig Cancer Research,University of Lausanne,Epalinges,Switzerland;[2]Department of Fundamental Oncology,University of Lausanne,Epalinges,Switzerland;[3]Department of Fundamental Oncology,University of Lausanne,Epalinges,Switzerland Ludwig Cancer Research Institute Lausanne Branch,Epalinges,Switzerland;[4]Center for Systems Medicine,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,100005,Beijing,China;[5]Suzhou Institute of Systems Medicine,Suzhou,Jiangsu,215123,China;[6]Center for Integrative Genomics,University of Lausanne,Lausanne,Switzerland

出　　处：《Cellular & Molecular Immunology》索引2021年第18卷第7期,共11页

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). 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 fitness.Specifically,memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands.In contrast,tumor-infiltrating lymphocytes(TILs)display severe metabolic defects,which may underlie their functional decline.Here,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 generation.PGC-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide vaccination.Importantly,CD8 T cells with enhanced PGC-1αexpression provide stronger antitumor immunity in a mouse melanoma model.Moreover,TILs overexpressing PGC-1αmaintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free host.Altogether,our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation,metabolic fitness,and antitumor immunity in vivo. 关键词：PGC-1Α MITOCHONDRIA CD8 MEMORY Anti-tumor immunity

相关文献

参考文献（32）
引证文献（7）
耦合文献（0）

参考文献(32)

引证文献(7)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

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

参考文献(32)

引证文献(7)

用户提示