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Updated: May 5, 2026

Preparation of Myeloid Derived Suppressor Cells MDSC from Naive and Pancreatic Tumor-bearing Mice using Flow Cytometry and Automated Magnetic Activated Cell Sorting AutoMACS
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Preparation of Myeloid Derived Suppressor Cells MDSC from Naive and Pancreatic Tumor-bearing Mice using Flow Cytometry and Automated Magnetic Activated Cell Sorting AutoMACS

Published on: June 18, 2012

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Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis

Jeremy D Waight, Colleen Netherby, Mary L Hensen

    The Journal of Clinical Investigation
    |October 5, 2013
    PubMed

    Insights

    Interferon regulatory factor-8 (IRF-8) deficiency drives the development of myeloid-derived suppressor cells (MDSCs). Restoring IRF-8 levels may offer new strategies to target MDSCs in cancer therapy.

    Area of Science:

    • Immunology
    • Cancer Biology
    • Molecular Biology

    Background:

    • Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that impair anti-tumor immunity and pose a barrier to cancer therapy.
    • The precise mechanisms governing MDSC development and their granulocytic bias remain incompletely understood.
    • Aberrant myelopoiesis, potentially linked to transcriptional regulators, is implicated in MDSC generation.

    Purpose of the Study:

    • To investigate the role of interferon regulatory factor-8 (IRF-8) in the development and regulation of MDSCs.
    • To determine if IRF-8 perturbations contribute to the aberrant myelopoiesis observed in MDSC populations.
    • To explore the therapeutic potential of modulating IRF-8 levels for cancer treatment.

    Main Methods:

    • Utilized Irf8-deficient mice to model MDSC development.
    • Overexpressed IRF-8 in mice to assess its impact on MDSC accumulation and immunotherapy.
    • Investigated the influence of G-CSF and GM-CSF on IRF-8 expression via STAT3 and STAT5 pathways.
    • Analyzed IRF-8 levels in MDSCs from breast cancer patients.

    Main Results:

    • Irf8-deficient mice exhibited myeloid populations phenotypically and functionally similar to tumor-induced MDSCs.
    • IRF-8 overexpression reduced MDSC accumulation and improved the efficacy of cancer immunotherapy.
    • Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) downregulated IRF-8 through STAT3/STAT5.
    • Decreased IRF-8 levels correlated with increased MDSC frequency in breast cancer patients.

    Conclusions:

    • IRF-8 acts as a critical negative regulator in the development of myeloid-derived suppressor cells.
    • Dysregulation of IRF-8 contributes to the expansion of MDSCs in neoplastic conditions.
    • Targeting IRF-8 presents a novel therapeutic strategy for overcoming MDSC-mediated immunosuppression in cancer.

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