NDLI: Interferon regulatory factor-8 modulates the development of tumour-induced CD11b+Gr-1+ myeloid cells

Content Provider	PubMed Central
Author	Stewart, Trina J. Greeneltch, Kristy M. Reid, Julia E. Liewehr, David J. Steinberg, Seth M. Liu, Kebin Abrams, Scott I.
Copyright Year	2009
Abstract	Tumour-induced myeloid-derived suppressor cells (MDSC) promote immune suppression and mediate tumour progression. However, the molecular basis for the generation of MDSC, which in mice co-express the CD11b+ and Gr-1+ cell surface markers remains unclear. Because CD11b+Gr-1+ cells expand during progressive tumour growth, this suggests that tumour-induced events alter signalling pathways that affect normal myeloid cell development. Interferon regulatory factor-8 (IRF-8), a member of the IFN-γ regulatory factor family, is essential for normal myelopoiesis. We therefore examined whether IRF-8 modulated tumour-induced CD11b+Gr-1+ cell development or accumulation using both implantable (4T1) and transgenic (MMTV-PyMT) mouse models of mammary tumour growth. In the 4T1 model, both splenic and bone marrow-derived CD11b+Gr-1+ cells of tumour-bearing mice displayed a marked reduction in IRF-8 expression compared to control populations. A causal link between IRF-8 expression and the emergence of tumour-induced CD11b+Gr-1+ cells was explored in vivo using a double transgenic (dTg) mouse model designed to express transgenes for both IRF-8 and mammary carcinoma development. Despite the fact that tumour growth was unaffected, splenomegaly, as well as the frequencies and absolute numbers of CD11b+Gr-1+ cells were significantly lower in dTg mice when compared with single transgenic tumour-bearing mice. Overall, these data reveal that IRF-8 plays an important role in tumour-induced development and/or accumulation of CD11b+Gr-1+ cells, and establishes a molecular basis for the potential manipulation of these myeloid populations for cancer therapy.
Related Links	http://dx.doi.org/10.1111/j.1582-4934.2009.00685.x
Ending Page	3950
Page Count	12
Starting Page	3939
File Format	PDF
ISSN	15821838
e-ISSN	15824934
Journal	Journal of Cellular and Molecular Medicine
Issue Number	9b
Volume Number	13
Language	English
Publisher	John Wiley & Sons, Ltd
Publisher Date	2009-09-01
Access Restriction	Open
Rights Holder	John Wiley & Sons, Ltd
Subject Keyword	Molecular Medicine Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Medicine

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