PLoS ONE (Jan 2018)

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

  • Jaclyn Sceneay,
  • Christoph M Griessinger,
  • Sabrina H L Hoffmann,
  • Shu Wen Wen,
  • Christina S F Wong,
  • Sophie Krumeich,
  • Manfred Kneilling,
  • Bernd J Pichler,
  • Andreas Möller

DOI
https://doi.org/10.1371/journal.pone.0196040
Journal volume & issue
Vol. 13, no. 4
p. e0196040

Abstract

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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.