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Series GSE32373 Query DataSets for GSE32373
Status Public on Sep 26, 2011
Title Gene expression analysis of OX40-triggered mouse Treg
Organism Mus musculus
Experiment type Expression profiling by array
Summary Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor.
 
Overall design Total RNA obtained from sorted mouse FoxP3-GFP+ Treg activated in vitro with anti-CD3 in the presence of an OX40-agonist mAb (OX86) or isotype control.
 
Contributor(s) Pittoni P, Burocchi A
Citation(s) 22229156
Submission date Sep 26, 2011
Last update date Jun 14, 2018
Contact name Paola Pittoni
E-mail(s) paola.pittoni@istitutotumori.mi.it
Phone +39 0223903232
Fax +39 0223902630
Organization name IRCCS Istituto Nazionale dei Tumori
Department Dept. Experimental Oncology
Lab Molecular Immunology Unit
Street address Via Amadeo, 42
City Milan
State/province Italy
ZIP/Postal code 20133
Country Italy
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (4)
GSM801458 Treg+iso rep1
GSM801459 Treg+OX86 rep1
GSM801460 Treg+iso rep2
Relations
BioProject PRJNA147975

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
GSE32373_RAW.tar 3.1 Mb (http)(custom) TAR
GSE32373_non-normalized_data.txt.gz 746.1 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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