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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods*
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Interleukin-6 / pharmacology*
  • Lymphocyte Activation
  • Mammary Neoplasms, Experimental / diagnostic imaging*
  • Mammary Neoplasms, Experimental / immunology
  • Mice
  • Myeloid-Derived Suppressor Cells / cytology*
  • Myeloid-Derived Suppressor Cells / immunology
  • Neoplasm Metastasis
  • Optical Imaging
  • Stem Cell Transplantation
  • Tumor Microenvironment

Substances

  • Interleukin-6
  • Granulocyte-Macrophage Colony-Stimulating Factor

Grants and funding

This work was supported by the Research Fellowship of the German Research Foundation (GR4017/1-1) and a Fortüne-Junior Grant (2309-0-0) of the Medical Faculty for CMG; the University of Tübingen and the Swiss Werner Siemens Foundation for BJP; the National Health and Medical Research Council Australia (NHMRC, APP1068510), Cancer Council Queensland (APP1045620) Rio-Tinto-Ride-To-Conquer-Cancer (6156), and National Breast Cancer Foundation (Australia) fellowship and grant to AM (ECF-11-09, NC-13-26). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.