GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE84468 Query DataSets for GSE84468
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.
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
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
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)
GSM2236767 poly(A) mRNA MDSC_wt_UT R1
GSM2236768 poly(A) mRNA MDSC_wt_UT R2
GSM2236769 poly(A) mRNA MDSC_wt_IFNg R1
BioProject PRJNA329282
SRA SRP078590

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
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 SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap