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| Status |
Public on Jul 05, 2013 |
| Title |
Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Interferon Regulatory Factor-8, an Integral Determinant of Myeloid-Derived Suppressor Cell Subset Development.
Myeloid-derived suppressor cells (MDSC) are a major barrier to anticancer responses. Although much is known about how MDSC promote tumor progression, little is known about how they develop. We hypothesized that MDSC develop as a consequence of tumor-induced downregulation of interferon regulatory factor-8 (IRF-8), a key myeloid developmental transcription factor. We showed that: 1) IRF8-deficiency in mice generated myeloid populations highly homologous to tumor-induced MDSC; 2) IRF-8 overexpression in mice reduced MDSC accumulation and retarded tumor growth; 3) MDSC-inducing factors, G-CSF or GM-CSF, facilitated IRF-8 downregulation via STAT3- or STAT5-dependent pathways, respectively; and 4) IRF-8 levels in MDSC-like subsets of breast cancer patients were depressed compared to healthy donors. Altogether, our data implicate IRF-8 as a novel MDSC-dependent transcription factor.
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| Overall design |
Splenic CD11b+Gr-1high cell populations from tumor-bearing mice, IRF8 knockout mice or non-tumor-bearing control mice were purified in two independent experiments by flow cytometry (> 97% purity) and subjected to whole genome expression profiling using Illumina microarrays.
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| Contributor(s) |
Waight JD, Hensen ML, Miller A, Hu Q, Liu S, Bogner P, Liu K, Abrams SI |
| Citation(s) |
24091328 |
| Submission date |
Jul 10, 2012 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Qiang Hu |
| E-mail(s) |
Qiang.Hu@RoswellPark.org
|
| Organization name |
Roswell Park Cancer Institute
|
| Street address |
Elm & Carlton Streets
|
| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14263 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (6)
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| GSM958404 |
IRF8 KO 2 |
| GSM958405 |
Wild type with tumor produced by AT-3 cell line 1 |
| GSM958406 |
Wild type with tumor produced by AT-3 cell line 2 |
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| Relations |
| BioProject |
PRJNA170253 |
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