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PLoS One. 2018 Apr 20;13(4):e0196040. doi: 10.1371/journal.pone.0196040. eCollection 2018.

Tracking the fate of adoptively transferred myeloid-derived suppressor cells in the primary breast tumor microenvironment.

Author information

1
Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.
2
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
3
Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
4
School of Medicine, University of Queensland, Brisbane, Australia.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid progenitor cells that are expanded in cancer and act as potent suppressors of the anti-tumor immune response. MDSCs consist of two major subsets, namely monocytic (M-) MDSCs and granulocytic (G-) MDSCs that differ with respect to their phenotype, morphology and mechanisms of suppression. Here, we cultured bone marrow cells with IL-6 and GM-CSF in vitro to generate a population of bone marrow MDSCs (BM-MDSCs) similar to G-MDSCs from tumor-bearing mice in regards to phenotype, morphology and suppressive-function. Through fluorescent labeling of these BM-MDSCs and optical imaging, we could visualize the recruitment and localization of BM-MDSCs in breast tumor-bearing mice in vivo. Furthermore, we were able to demonstrate that BM-MDSCs home to primary and metastatic breast tumors, but have no significant effect on tumor growth or progression. Ex vivo flow cytometry characterization of BM-MDSCs after adoptive transfer demonstrated both organ-and tumor-specific effects on their phenotype and differentiation, demonstrating the importance of the local microenvironment on MDSC fate and function. In this study, we have developed a method to generate, visualize and detect BM-MDSCs in vivo and ex vivo through optical imaging and flow cytometry, in order to understand the organ-specific changes rendered to MDSCs in breast cancer.

PMID:
29677215
PMCID:
PMC5909918
DOI:
10.1371/journal.pone.0196040
[Indexed for MEDLINE]
Free PMC Article

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