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Series GSE199177 Query DataSets for GSE199177
Status Public on Nov 10, 2022
Title The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Type I Interferons (IFN-I) stimulate pro-inflammatory programs critical for immune activation, but also induce immune-suppressive feedback circuits that contribute to the failure of cancer control. Yet, how IFN-Is differentially induce these opposing programs remains enigmatic. We establish that the transcription factor Interferon Regulatory Factor 2 (IRF2) is a central feedback molecule attenuating IFN signaling and driving CD8 T cell exhaustion in the tumor microenvironment. IRF2 inhibits CD8 T cell effector function in response to sustained interferon signaling by programming T cell exhaustion. Lineage-specific deletion of IRF2 limits CD8 T cells exhaustion to maintain effector functions, thereby enabling long-term tumor control, and increased responsiveness to immune-checkpoint and adoptive cell therapies. Long-term tumor control by IRF2-deficient CD8 T cells is dependent on continuous integration of both IFN-I and IFN? signals, which in the absence of IRF2, potentiate sustained effector function instead of exhaustion. Thus, IRF2 redirects IFN signalling to drive T cell exhaustion and prevent tumor control.
Overall design For AB-Seq experiment, MC38 Tumor-infitrating CD8 T cells from WT (Tumor WT), Irf2-/- (Tumor IRF2KO) mice. For scATAC-Seq experiment, MC38 Tumor-infitrating CD8 T cells from WT (Tumor WT), Irf2-/- (Tumor Irf2-/-) mice, as well as MC38 Tumor-infitrating CD8 T cells from mice that only lack IRF2 expression in the CD8 T cells (termed Tumor CD8-IRF2cKO mice) together with their controls Tumor CD8-IRF2cWT). For CUT&Tag - Naive isolated CD8+ T cells were isolated and invitro activated using anti-CD3 and Anti-CD28 and subjecte to either anti-IRF2 or IgG antibodies.
Web link
Contributor(s) Lukhele S, Abd Rabbo D, Guo M, Shen J, Elsaesser HJ, Carew M, Gadalla R, Quevedo R, Snell LM, Ciudad TM, Snow BE, You-Ten A, Haight J, Wakeham A, Ohashi PS, Mak TW, Cui W, McGaha TL, Brooks DG
Citation(s) 36370712
Submission date Mar 22, 2022
Last update date Nov 16, 2022
Contact name David Brooks
Organization name Princess Margaret Cancer Centre
Street address 610, University Ave
City Toronto
ZIP/Postal code M5G 2C1
Country Canada
Platforms (2)
GPL21626 NextSeq 550 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM5965785 WT_GEX
GSM5965786 IRF2_KO_GEX
GSM6619562 Tumor WT
BioProject PRJNA818703

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
GSE199177_RAW.tar 2.7 Gb (http)(custom) TAR (of TAR)
GSE199177_WT_n_IRF2.KO_CD8_T_cells.h5Seurat 27.0 Mb (ftp)(http) H5SEURAT
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Raw data are available in SRA
Processed data are available on Series record

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