|
| Status |
Public on May 15, 2020 |
| Title |
Tumor-derived prostaglandin E2 promotes p50 NF-κB-dependent differentiation of monocytic MDSC. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and hinder the effectiveness of anti-cancer treatments. Of note, in response to interferon-γ (IFNγ) M-MDSC release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express anti-tumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSC, diverting their response to IFNγ towards NO-mediated immunosuppression and reducing TNFα expression. At the genome level, p50 NF-κB promoted binding of STAT1 to regulatory regions of selected IFNγ-dependent genes, including inducible nitric oxide synthase (Nos2). In agreement, ablation of p50 as well as pharmacological inhibition of either the PGE2 receptor EP2 or NO production reprogrammed M-MDSC towards a NOS2low/TNFαhigh phenotype, restoring the in vivo antitumor activity of IFNγ. Our results indicate that inhibition of the PGE2/p50/NO axis prevents MDSC suppressive functions and restores the efficacy of anticancer immunotherapy.
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| |
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| Overall design |
Poly(A) RNA capture followed by multiparallel sequencing performed in Monocytic Myeloid Derived Suppressor Cells (M-MDSC) or Peritoneal Exudate Macrophages (PEC) from wild-type and p50ko mice
Chromatin immuno-precipitations of the transcription factor Stat1 in PECs followed by multiparallel sequencing
|
| Web link |
https://www.ncbi.nlm.nih.gov/pubmed/32265223
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| |
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| Contributor(s) |
Porta C, Piccolo V, Consonni F, Ostuni R, Soldà G, Natoli G, Sica A |
| Citation(s) |
32265223 |
| |
| Submission date |
Jul 15, 2016 |
| Last update date |
May 16, 2020 |
| Contact name |
Viviana Piccolo |
| E-mail(s) |
[email protected]
|
| Organization name |
European Institute of Oncology (IEO)
|
| Department |
Department of Experimental Oncology
|
| Lab |
Gioacchino Natoli Lab
|
| Street address |
Via Adamello 16
|
| City |
Milano |
| State/province |
Milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
| |
|
| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (20)
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|
| Relations |
| BioProject |
PRJNA329282 |
| SRA |
SRP078590 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84468_PECs_WT_IFNg_vs_INPUT_Fix_Norm.bigWig |
237.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE84468_PECs_WT_IFNg_vs_INPUT_peaks.bed.gz |
911.5 Kb |
(ftp)(http) |
BED |
| GSE84468_PECs_WT_UT_vs_INPUT_Fix_Norm.bigWig |
337.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE84468_PECs_WT_UT_vs_INPUT_peaks.bed.gz |
45.9 Kb |
(ftp)(http) |
BED |
| GSE84468_PECs_p50ko_IFNg_vs_INPUT_peaks.bed.gz |
812.4 Kb |
(ftp)(http) |
BED |
| GSE84468_PECs_p50ko_UT_vs_INPUT_peaks.bed.gz |
210.6 Kb |
(ftp)(http) |
BED |
| GSE84468_PECs_p52ko_IFNg_vs_INPUT_Fix_Norm.bigWig |
259.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE84468_PECs_p52ko_UT_vs_INPUT_Fix_Norm.bigWig |
328.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE84468_Standard_CPM_MDSC.txt.gz |
563.8 Kb |
(ftp)(http) |
TXT |
| GSE84468_Standard_CPM_PECs.xls.gz |
2.5 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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