Dataset Information

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.

SUBMITTER: Hart KM

PROVIDER: S-EPMC4211619 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.

Hart Kevin M KM Usherwood Edward J EJ Berwin Brent L BL

Immunology and cell biology 20140311 6

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 nongranulocy ...[more]

PMID: 24613975

Similar Datasets

Project description:The presence of tumor infiltrating lymphocytes (TILs) is associated with a longer overall survival in advanced stage epithelial ovarian cancer. Despite the prognostic impact of TILs, response to checkpoint-inhibitors and antigen-specific active immunotherapy is limited in ovarian cancer. The goal of our study was to investigate the interaction between ovarian cancer and the innate and adaptive immune system in the ID8-fLuc syngeneic ovarian cancer mouse model. For the in vivo experiments C57BL/6, B6.129S7-Rag1tm1Mom/J, and B6.129P2(SJL)-Myd88tm1.1Defr/J mice were inoculated with ID8-fLuc. In vivo depletion experiments were performed using clodronate liposomes (CL), anti-CD8a, anti-GR1, anti-colony stimulating factor 1 (anti-CSF1), and TMβ1 (anti-CD122). Immune read out was performed by fluorescent activated cell sorting analysis for effector T cells, regulatory T cells, natural killer cells, B cells, macrophages, and myeloid derived suppressor cells (MDSC), immunohistochemistry for MDSC and tumor-associated macrophages (TAM) and immunofluorescence for M1 and M2 TAM in the vascular context. The effect of MDSC on T cell proliferation and phenotype were studied in vitro. We discovered that the absence of T and B cells did not influence tumor growth or survival of B6.129S7-Rag1tm1Mom/J mice compared to immunocompetent C57BL/6 mice. CL-induced macrophage depletion promoted tumor proliferation and shortened survival in C57BL/6 mice (p = 0.004) and in B6.129S7-Rag1tm1Mom/J mice (p = 0.0005). During CL treatment, we observed a clear increase of pro-inflammatory cytokines (p ≤ 0.02) and monocytic MDSC (p ≤ 0.01). Selective depletion of MDSC by anti-GR1 improved survival, certainly in comparison to mice treated with anti-CSF1 (p = 0.01-median survival 91 vs. 67.5 days). B6.129P2(SJL)-Myd88tm1.1Defr/J mice displayed to a longer median survival compared to C57BL/6 mice (90 vs. 76 days). MDSC activated by ID8-fLuc conditioned medium or ascites of tumor-bearing mice showed T cell suppressive functions in vitro. Based on these findings, we conclude that the adaptive immune system does not efficiently control tumor growth in the ID8-fLuc model. In addition, we discovered a prominent role for MDSC as the driver of immunosuppression in the ID8-fLuc ovarian cancer mouse model.

Dataset Information

CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.

Publications

CX3CR1 delineates temporally and functionally distinct subsets of myeloid-derived suppressor cells in a mouse model of ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets