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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
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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.
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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.
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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
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Phone |
86-21-54237821
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Organization name |
Fudan Univ, Shanghai, China
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Department |
Institutes of Biomedical Sciences
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Lab |
Epigenetics lab
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Street address |
Dongan Road 131, Rm 511 Mingdao Building
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City |
Shanghai |
State/province |
Shanghai |
ZIP/Postal code |
200032 |
Country |
China |
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Platforms (1) |
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Samples (28)
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Relations |
BioProject |
PRJNA604913 |
SRA |
SRP247347 |