dc.contributor.author | J. Stewart, Trina | |
dc.contributor.author | J. Liewehr, David | |
dc.contributor.author | M. Steinberg, Seth | |
dc.contributor.author | M. Greeneltch, Kristy | |
dc.contributor.author | I. Abrams, Scott | |
dc.date.accessioned | 2017-05-03T16:13:13Z | |
dc.date.available | 2017-05-03T16:13:13Z | |
dc.date.issued | 2009 | |
dc.date.modified | 2013-06-13T23:24:41Z | |
dc.identifier.issn | 00221767 | |
dc.identifier.doi | 10.4049/jimmunol.0804132 | |
dc.identifier.uri | http://hdl.handle.net/10072/47231 | |
dc.description.abstract | CD11b Gr-1 -expressing cells, termed myeloid-derived suppressor cells, can mediate immunosuppression and tumor progression. However, the intrinsic molecular events that drive their protumorigenic behavior remain to be elucidated. Although CD11b Gr-1 cells exist at low frequencies in normal mice, it also remains unresolved whether they are biologically distinct from those of tumor-bearing hosts. These objectives were investigated using CD11b Gr-1 cells from both implantable (4T1) and autochthonous (mouse mammary tumor virus-polyomavirus middle T Ag (MMTV-PyMT)) mouse models of mammary carcinoma. Limited variation was observed in the expression of markers associated with immunoregulation between CD11b Gr-1 cells of both tumor models, as well as with their respective controls (Cnt). Despite limited differences in phenotype, tumor-induced CD11b Gr-1 cells were found to produce a more immunosuppressive cytokine profile than that observed by Cnt CD11b Gr-1 cells. Furthermore, when admixed with tumor cells, CD11b Gr-1 cells from tumor-bearing mice significantly enhanced neoplastic growth compared with counterpart cells from Cnt mice. However, the protumorigenic behavior of these tumor-induced CD11b Gr-1 cells was significantly diminished when the expression of IFN regulatory factor 8, a key myeloid-associated transcription factor, was enhanced. The loss of this protumorigenic effect occurred independently of the host immune system and correlated with a CD11b Gr-1 cytokine/chemokine production pattern that resembled cells from nontumor-bearing Cnt mice. Overall, our data indicate that 1) tumor-induced CD11b Gr-1 cells from both cancer models were phenotypically similar, but biologically distinct from their nontumor-bearing counterparts and 2) modulation of IFN regulatory factor 8 levels in tumor-induced CD11b Gr-1 cells can significantly abrogate their protumorigenic behavior, which may have important implications for cancer therapy. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Association of Immunologists | |
dc.publisher.place | United States | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 117 | |
dc.relation.ispartofpageto | 128 | |
dc.relation.ispartofissue | 1 | |
dc.relation.ispartofjournal | Journal of Immunology | |
dc.relation.ispartofvolume | 183 | |
dc.rights.retention | Y | |
dc.subject.fieldofresearch | Tumour Immunology | |
dc.subject.fieldofresearch | Immunology | |
dc.subject.fieldofresearchcode | 110709 | |
dc.subject.fieldofresearchcode | 1107 | |
dc.title | Modulating the Expression of IFN Regulatory Factor 8 Alters the Protumorigenic Behavior of CD11b+Gr-1+ Myeloid Cells | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.rights.copyright | Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author for more information. | |
gro.date.issued | 2009 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Stewart, Trina | |