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Series GSE110523 Query DataSets for GSE110523
Status Public on Aug 11, 2020
Title miR-24 induces human T cell exhaustion though mitochondria energy metabolic reprograming via suppressing MYC and FGF11
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Exhausted T cells (TExh) is a barrier for cancer immunotherapy, evidences demonstrate that transcriptional regulation is essential for TEX induction; however the factors that manipulate exhausted phenotype are largely unexplored. Here we showed that the microRNA (miR)-24, previously established to be enriched in eoxosmes from nasopharyngeal carcinoma (NPC) cells and promote T cell dysfunction, induced T cells to express high level of TIM-3, PD-1 and CD39 but to display low IFNg and GrB secretion and diminished proliferation ability ( a TExh phenotype) through inhibiting energy metabolism in vitro. Forced miR-24 expression inhibited ATP production through mitochondrial oxidative phosphorylation, while blockade of endogenous miR-24 the mitochondrial formation became massive and tubular and the levels of mitochondrial constituent proteins including Mfn1, Mfn2, P-Drp1 and TOMM20 was increased in OKT-3 stimulated T cells. MiR-24-mediated TEX and mitochondria metabolism reprogramming were regulated by suppressing MYC and FGF11 expression. Moreover, MYC enhanced the FGF11 transcription to promote mitochondria ATP production. Importantly, clinical data showed an increased TEX phenotype in circuiting and tumor-infiltrating T cells from NPC patients. Thus, our findings support that inhibition of miR-24-mediated mitochondria metabolism reprogramming can be titrated to break TExh immune barrier in NPC immunotherapy.
Overall design Examination of 2 different treatments in human T cells.
Contributor(s) Li J, Liu Y
Citation(s) 32973789
Submission date Feb 13, 2018
Last update date Sep 28, 2020
Contact name Jiang Li
Organization name State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center
Street address Dongfengdong Road NO.651, Yuexiu District
City Guangzhou
State/province Guangdong
ZIP/Postal code 510060
Country China
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (4)
GSM2995189 T cell_cont
GSM2995190 T cell_mir24
GSM2995191 T cell_mir24_sponge_cont
BioProject PRJNA433927
SRA SRP132772

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Supplementary file Size Download File type/resource
GSE110523_miR24--miR24_sponge.all.gene.txt.gz 657.3 Kb (ftp)(http) TXT
GSE110523_mir24-cont-analyzed.txt.gz 1.2 Mb (ftp)(http) TXT
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