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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 30, 2021 |
| Title |
Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion [BiSulfite-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Glioblastoma multiforme (GBM) is an aggressive brain tumour. Current immunotherapy approaches have been unsuccessful, highlighting the need to determine underlying mechanisms of immune evasion. Here, we developed syngeneic immunocompetent mouse models of GBM to explore this. GBM stem cells (GSCs) were serially transplanted through immunocompetent hosts, which uncovered an acquired capability to escape immune clearance through an enhanced immunosuppressive tumour microenvironment. Mechanistically, this was not elicited via genetic selection of tumour subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack. These include activation of interferon signalling modules, myeloid-affiliated transcription factors and chemokines, which leads to increased recruitment of tumour-associated macrophages. Furthermore, we identify similar epigenetic and transcriptional signatures in human mesenchymal subtype GSCs. We conclude that epigenetic immunoediting may drive an acquired immune evasion program in the most aggressive mesenchymal GBM subtype by reshaping the tumour immune microenvironment.
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| Overall design |
WT BL6, and engineered mouse neural stem cells with common GBM driver mutations in double and triple combinations (NP, NPE), profiled by RRBS.
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| Contributor(s) |
Southgate B, Bradley L, Pollard SM |
| Citation(s) |
33857425 |
| Submission date |
Jan 23, 2021 |
| Last update date |
May 19, 2021 |
| Contact name |
Ben Southgate |
| Organization name |
University of Edinburgh
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| Street address |
Little France Dr
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| City |
Edinburgh |
| ZIP/Postal code |
EH16 4UU |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (27)
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| GSM5032687 |
WT rep4 [BiSulfite-seq] |
| GSM5032688 |
WT rep5 [BiSulfite-seq] |
| GSM5032689 |
WT rep6 [BiSulfite-seq] |
| GSM5032690 |
Nf1 KO, Pten KO rep1 [BiSulfite-seq] |
| GSM5032691 |
Nf1 KO, Pten KO rep2 [BiSulfite-seq] |
| GSM5032692 |
Nf1 KO, Pten KO rep3 [BiSulfite-seq] |
| GSM5032693 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep1 [BiSulfite-seq] |
| GSM5032694 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep2 [BiSulfite-seq] |
| GSM5032695 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep3 [BiSulfite-seq] |
| GSM5032696 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep4 [BiSulfite-seq] |
| GSM5032697 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep5 [BiSulfite-seq] |
| GSM5032698 |
Nf1 KO, Pten KO, EGFRvIII overexpression rep6 [BiSulfite-seq] |
| GSM5032699 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from NSG mouse rep1 [BiSulfite-seq] |
| GSM5032700 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from NSG mouse rep2 [BiSulfite-seq] |
| GSM5032701 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from NSG mouse rep3 [BiSulfite-seq] |
| GSM5032702 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep1 [BiSulfite-seq] |
| GSM5032703 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep2 [BiSulfite-seq] |
| GSM5032704 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep3 [BiSulfite-seq] |
| GSM5032705 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep4 [BiSulfite-seq] |
| GSM5032706 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep5 [BiSulfite-seq] |
| GSM5032707 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Tumour derived from BL6 mouse rep6 [BiSulfite-seq] |
| GSM5032708 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Twice Tumour derived BL6 mouse, Immune evasive rep1 [BiSulfite-seq] |
| GSM5032709 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Twice Tumour derived BL6 mouse, Immune evasive rep2 [BiSulfite-seq] |
| GSM5032710 |
Nf1 KO, Pten KO, EGFRvIII overexpression, Twice Tumour derived BL6 mouse, Immune evasive rep3 [BiSulfite-seq] |
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| This SubSeries is part of SuperSeries: |
| GSE165391 |
Glioblastoma cells acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion |
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| Relations |
| BioProject |
PRJNA694305 |
| SRA |
SRP302974 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE165389_RRBS_M_methylation.txt.gz |
36.3 Mb |
(ftp)(http) |
TXT |
| GSE165389_RRBS_T_methylation.txt.gz |
37.7 Mb |
(ftp)(http) |
TXT |
| GSE165389_RRBS_percent_methylation.txt.gz |
79.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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