AUTHOR=Liu Yi-Na , Yang Jie-Feng , Huang Dai-Jia , Ni Huan-He , Zhang Chuan-Xia , Zhang Lin , He Jia , Gu Jia-Mei , Chen Hong-Xia , Mai Hai-Qiang , Chen Qiu-Yan , Zhang Xiao-Shi , Gao Song , Li Jiang TITLE=Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01906 DOI=10.3389/fimmu.2020.01906 ISSN=1664-3224 ABSTRACT=
T cell exhaustion is an obstacle to immunotherapy for solid tumors. An understanding of the mechanism by which T cells develop this phenotype in solid tumors is needed. Here, hypoxia, a feature of the tumor microenvironment, causes T cell exhaustion (TExh) by inducing a mitochondrial defect. Upon exposure to hypoxia, activated T cells with a TExh phenotype are characterized by mitochondrial fragmentation, decreased ATP production, and decreased mitochondrial oxidative phosphorylation activity. The TExh phenotype is correlated with the downregulation of the mitochondrial fusion protein mitofusin 1 (MFN1) and upregulation of miR-24. Overexpression of miR-24 alters the transcription of many metabolism-related genes including its target genes