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.
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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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.
A systemic response to severe infection or tissue damage that leads to a hyperactive and unbalanced network of pro-inflammatory mediators. Vascular permeability, cardiac function and metabolic balance are affected, resulting in tissue necrosis, multi-organ failure and death.
- Complete Freund's adjuvant
An oil that contains an emulsifying agent and killed mycobacteria, which increase the immune response to an immunogen. For administration, a water-in-oil emulsion is made with a solution that contains the immunogen of interest.
- Experimental autoimmune encephalomyelitis
(EAE). An animal model of the human autoimmune disease multiple sclerosis. EAE is induced in experimental animals by immunization with myelin or peptides that are derived from myelin. The animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord.
The process of differentiation of common myeloid progenitor cells to polymorphonuclear leukocytes and monocytes.
- Tumour immunosurveillance
The process of recognition of tumour antigens and elimination of the tumours by the immune system.
- T-cell anergy
A state of T-cell unresponsiveness to stimulation with antigen. It can be induced by stimulation with a large amount of specific antigen in the absence of the engagement of co-stimulatory molecules.
- Regulatory T (TReg) cells
A specialized type of CD4+ T cell that can suppress the responses of other immune cells. These cells provide a crucial mechanism for the maintenance of peripheral self tolerance and are characterized by the expression of CD25 and the transcription factor forkhead box P3.
- Tumour-associated macrophage
A cell that differentiates from circulating blood monocytes and myeloid-derived suppressor cells that have infiltrated tumours. These cells can have positive or negative effects on tumorigenesis.
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Cite this article
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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