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| 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.
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| 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.
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| 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 |
| |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA147975 |
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