title: CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.
abstract: Expression of the chemokine receptor CX3CR1 has been used to identify distinct populations within the monocyte, macrophage and dendritic cell lineages. Recent evidence indicates that CX3CR1-positive subsets of myeloid cells play distinct and important roles in a wide range of immunological maladies, and thus the use of CX3CR1 expression has leveraged our understanding of the myeloid contribution to a multitude of diseases. Here we use CX3CR1 expression as a means to identify a novel nongranulocytic CX3CR1-negative myeloid population that is functionally distinct from the previously described CX3CR1-positive cellular subsets within the CD11b-positive cellular compartment of ascites from ovarian tumor-bearing mice. We functionally identify CX3CR1-negative cells as myeloid suppressor cells and as a cellular subset with pathological specificity. Importantly, the CX3CR1-negative cells exhibit early IL-10 production in the ovarian tumor microenvironment, which we have shown to be critically tied to suppression and additional myeloid-derived suppressor cell accumulation, and we now show that this cellular population actively contributes to tumor progression. Furthermore, we demonstrate that the CX3CR1-negative population is derived from the recently described CX3CR1-positive macrophage/dendritic cell precursor cell. These studies provide a greater understanding of the generation and maintenance of regulatory myeloid subsets and have broad implications for the elucidation of myeloid function and contributions within the tumor microenvironment.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical Center, Lebanon, NH, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hart
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical Center, Lebanon, NH, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Usherwood
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical Center, Lebanon, NH, USA.
authors.forename: Brent L
authors.initials: BL
authors.lastname: Berwin
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D005260:Female; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C556062:IL10 protein, mouse; D019707:Receptors, Chemokine; D016753:Interleukin-10