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

• Published in: PloS one 2018-04, Vol.13 (4), p.e0196040-e0196040
• Main Authors: Sceneay, Jaclyn, Griessinger, Christoph M, Hoffmann, Sabrina H L, Wen, Shu Wen, Wong, Christina S F, Krumeich, Sophie, Kneilling, Manfred, Pichler, Bernd J, Möller, Andreas
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Antigens; Biology and Life Sciences; Bone marrow; Breast cancer; Cancer; Cancer metastasis; Cells (biology); Cytokines; Cytometry; Dendritic cells; Development and progression; Flow cytometry; Fluorescence; Genetic aspects; Granulocyte-macrophage colony-stimulating factor; Granulocytes; Immune response; Immune system; In vivo methods and tests; Interleukin 6; Laboratories; Localization; Lymphocytes; Medical research; Medicine and Health Sciences; Metastases; Metastasis; Mice; Monocytes; Morphology; Phenotypes; Physiological aspects; Population; Progenitor cells; Research and Analysis Methods; Stem cells; Suppressor cells; Suppressors; T cell receptors; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196040

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.