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  • Review Article
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Myeloid-derived suppressor cells as regulators of the immune system

Nature Reviews Immunology volume 9, pages 162–174 (2009)Cite this article

Key Points

  • Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells of myeloid origin.

  • MDSCs expand during various pathological conditions, including cancer, inflammation and trauma, and are characterized by the increased production of reactive oxygen and nitrogen species, and by arginase 1 activity.

  • Two subsets of MDSCs have been identified based on their morphology and cell-surface expression of specific molecules. The granulocytic subset has a CD11b+LY6G+LY6Clow phenotype and the monocytic subset has a CD11b+LY6G−LY6Chi phenotype. Although both subsets can suppress T cells, their mechanisms of suppression are different.

  • The expansion of MDSCs is promoted by numerous factors that include prostaglandins, stem-cell factor, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, interleukin-6 (IL-6) and vascular endothelial growth factor.

  • The expansion of MDSCs in pathological conditions is associated with their activation. The main factors that cause MDSC activation are interferon-γ, ligands for Toll-like receptors, IL-4, IL-13 and transforming growth factor-β.

  • Immunosuppressive functions of MDSCs require direct cell–cell contact and can result in antigen-specific or antigen-non-specific suppression of T-cell responses.

  • Arginase 1, inducible nitric oxide synthase, reactive oxygen species and peroxynitrite are thought to have a role in MDSC-mediated T-cell suppression.

  • Agents that may be effective for targeting MDSCs for therapy include all-trans retinoic acid, amino-bisphosphonates, inhibitors of cyclooxygenase 2 and phosphodiesterase 5, and some chemotherapeutic drugs.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand during cancer, inflammation and infection, and that have a remarkable ability to suppress T-cell responses. These cells constitute a unique component of the immune system that regulates immune responses in healthy individuals and in the context of various diseases. In this Review, we discuss the origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit.

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Figure 1: The origin of MDSCs.
Figure 2: Signalling pathways involved in the expansion of MDSCs.
Figure 3: Suppressive mechanisms mediated by different subsets of MDSCs.
Figure 4: The mechanisms of MDSC-mediated immune suppression differ in peripheral lymphoid organs and at the site of a tumour.

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Acknowledgements

We thank the members of the Gabrilovich laboratory for their contributions. We apologize to those colleagues whose data we could not cite owing to space limitations.

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Authors and Affiliations

  1. and Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida, 33612, USA.,

    Dmitry I. Gabrilovich & Srinivas Nagaraj

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  1. Dmitry I. Gabrilovich
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  2. Srinivas Nagaraj
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Correspondence to Dmitry I. Gabrilovich.

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Gabrilovich, D., Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9, 162–174 (2009). https://doi.org/10.1038/nri2506

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