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Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

Nature Reviews Immunology volume 21, pages 485–498 (2021)Cite this article

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Abstract

Myeloid-derived suppressor cells (MDSCs) are pathologically activated neutrophils and monocytes with potent immunosuppressive activity. They are implicated in the regulation of immune responses in many pathological conditions and are closely associated with poor clinical outcomes in cancer. Recent studies have indicated key distinctions between MDSCs and classical neutrophils and monocytes, and, in this Review, we discuss new data on the major genomic and metabolic characteristics of MDSCs. We explain how these characteristics shape MDSC function and could facilitate therapeutic targeting of these cells, particularly in cancer and in autoimmune diseases. Additionally, we briefly discuss emerging data on MDSC involvement in pregnancy, neonatal biology and COVID-19.

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Fig. 1: Distinguishing MDSCs from classical neutrophils and monocytes.
Fig. 2: Metabolic characteristics of MDSCs.
Fig. 3: Contribution of MDSCs to the formation of the premetastatic niche.
Fig. 4: Targeting MDSCs in cancer and autoimmune diseases.

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Acknowledgements

The authors thank S. Gabrilovich, Rutgers New Jersey Medical School, for help with editing the manuscript.

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  1. These authors contributed equally: Filippo Veglia, Emilio Sanseviero.

Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Filippo Veglia

  2. Wistar Institute, Philadelphia, PA, USA

    Emilio Sanseviero

  3. AstraZeneca, Gaithersburg, MD, USA

    Dmitry I. Gabrilovich

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  1. Filippo Veglia
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  2. Emilio Sanseviero
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Glossary

Monocyte-like precursor of granulocytes

Recently identified population of monocytic precursors of granulocytes (primarily polymorphonuclear myeloid-derived suppressor cells (MDSCs)) accumulated in tumour-bearing hosts.

S100A8/A9

Heterodimer, calcium binding pro-inflammatory protein that presents in neutrophils and monocytes and greatly accumulates in MDSCs; it is considered as one of the hallmarks of these cells.

M1/M2 polarized macrophages

‘M1’ and ‘M2’ are classifications historically used to define macrophages activated in vitro as pro-inflammatory (when ‘classically’ activated with IFNγ and lipopolysaccharides) or anti-inflammatory (when ‘alternatively’ activated with IL-4 or IL-10), respectively. However, in vivo macrophages are highly specialized, transcriptomically dynamic and extremely heterogeneous with regards to their phenotypes and functions, which are continuously shaped by their tissue microenvironment. Therefore, the M1 or M2 classification is too simplistic to explain the true nature of in vivo macrophages, although these terms are still often used to indicate whether the macrophages in question are more pro-inflammatory or anti-inflammatory.

Methylglyoxal

CH3C(O)CHO is a reduced derivative of pyruvic acid involved in the formation of advanced glycation end products.

STING

Stimulator of interferon genes (STING) induces type I interferon production.

Lactoferrin

A globular glycoprotein from the transferrin family widely expressed in various secretory fluids such as milk, saliva, tears and nasal secretions.

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Veglia, F., Sanseviero, E. & Gabrilovich, D.I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol 21, 485–498 (2021). https://doi.org/10.1038/s41577-020-00490-y

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