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Series GSE144787 Query DataSets for GSE144787
Status Public on Aug 04, 2020
Title TET2 promotes anti-tumor immunity by governing G-MDSCs and CD8+ T cell numbers
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a pivotal role of the DNA demethylase and tumor suppressor TET2 played in host antitumor immunity. Deletion of Tet2 dramatically elevated the IL-6 level in Tet2-/- mice upon tumor challenge. The elevated IL-6 greatly stimulated the immunosuppressive granulocytic myeloid-derived suppressor cells (G-MDSCs), which in turn significantly reduced CD8+ T cells upon tumor challenge. Consequently, systematic knockout of the Tet2 in mice led to accelerated syngeneic tumor growth, which was constrained by anti-PD-1 blockade. Removal of G-MDSCs by the anti-mouse Ly6g Ab restored the numbers of CD8+ T cells in Tet2-/- mice and rebooted their anti-tumor activity. Importantly, anti-IL-6 Ab treatment blocked the expansion of G-MDSCs and inhibited syngeneic tumor growth. Collectively, these findings reveal a TET2-mediated IL-6/G-MDSC/CD8+ T immune response cascade that safeguards host adaptive anti-tumor immunity, offering a cell non-autonomous mechanism of TET2 for tumor suppression.
 
Overall design Identifying the differential expression genes between Tet2-KO and WT in syngeneic tumors and gMDSCs, and examining the 5mC and 5hmC profile of Tet2-KO and WT gMDSC in tumor bearing mice.

Please note that the *mr.txt.gz processed data was generated from each BS and OxBS pair sample and is linked to the corresponding *-BS sample records.
 
Contributor(s) Wu F, Li S, Feng J
Citation(s) 32929842
Submission date Feb 05, 2020
Last update date Nov 05, 2020
Contact name Feizhen Wu
E-mail(s) wufz@fudan.edu.cn
Phone 86-21-54237821
Organization name Fudan Univ, Shanghai, China
Department Institutes of Biomedical Sciences
Lab Epigenetics lab
Street address Dongan Road 131, Rm 511 Mingdao Building
City Shanghai
State/province Shanghai
ZIP/Postal code 200032
Country China
 
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (28)
GSM4296341 Hepa1-6_Tu_WT-1
GSM4296342 Hepa1-6_Tu_KO-1
GSM4296343 Hepa1-6_Tu_WT-2
Relations
BioProject PRJNA604913
SRA SRP247347

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE144787_RAW.tar 528.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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