Myeloid-Derived Suppressor Cells

Parker, Katherine H.; Beury, Daniel W.; Ostrand‐Rosenberg, Suzanne

doi:10.1016/bs.acr.2015.04.002

Cited by 429 publications

(252 citation statements)

References 194 publications

(231 reference statements)

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“…They (i) inhibit the activation of tumor-reactive T cells through their production of reactive oxygen and nitrogen species and by sequestering or degrading amino acids that are essential for T cell function, (ii) polarize immunity and macrophages toward a type 2 phenotype that supports tumor growth, (iii) prevent naive T cells from entering lymph nodes and becoming activated by down-regulating T cell expression of L-selectin, (iv) inhibit the cytotoxic activity of natural killer cells, (v) promote neovascularization through their production of vascular endothelial growth factor (VEGF), and (vi) promote metastasis through their production of matrix metalloproteases. 14 The inflammatory milieu present in most solid tumors exacerbates both the quantity and potency of MDSCs and induces their differentiation and accumulation from hematopoietic progenitor cells. 15–17 MDSCs mediate most of their immune suppressive and tumor-promoting functions within the tumor microenvironment (TME).…”

Section: Introductionmentioning

confidence: 99%

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Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function

et al. 2016

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In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs. We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs. These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells. As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets. The “don’t eat me” molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected. Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, MDSC function requires that the cells migrate from the bone marrow where they are generated into solid tumors. 14 …”

Section: Introductionmentioning

confidence: 99%

Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function

et al. 2016

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“…MDSCs are a heterogeneous population of immature myeloid cells and myeloid progenitor cells [31-34]. Under physiological situations, these immature cells would normally give rise to myeloid cells such as granulocytes, macrophages and dendritic cells, however under conditions of stress, such as in infection, trauma, autoimmune diseases and cancer, a block in their usual differentiation pathway leads to the expansion of immature myeloid cells [31, 33, 34].…”

Section: Origin and Subtypes Of Mdscsmentioning

confidence: 99%

Immature myeloid cells in the tumor microenvironment: Implications for immunotherapy

Kamran

Chandran

Löwenstein

et al. 2018

Clinical Immunology

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Various preclinical studies have demonstrated that the success of immunotherapeutic strategies in inhibiting tumor progression in animal models of Glioblastoma multiforme (GBM). It is also evident that tumor-induced immune suppression drastically impacts the efficacy of immune based therapies. Among the mechanisms employed by GBM to induce immunosuppression is the accumulation of regulatory T cells (Tregs) and Myeloid derived suppressor cells (MDSCs). Advancing our understanding about the pathways regulating the expansion, accumulation and activity of MDSCs will allow for the development of therapies aimed at abolishing the inhibitory effect of these cells on immunotherapeutic approaches. In this review, we have focused on the origin, expansion and immunosuppressive mechanisms of MDSCs in animal models and human cancer, in particular GBM.

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“…The MDSCs are a heterogeneous population of immature myeloid cells that are known to suppress the effects of the adaptive immune system and T-cell responses in particular. 10,11 The role of MDSCs in suppressing inflammation-related diseases has a been demonstrated in patients with cancer, 12 autoimmune disease, 13 as well as chronic infection and inflammatory bowel disease.…”

Section: Article See P 858mentioning

confidence: 99%

The Good and the Bad

Hay

2015

Circulation Research

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EditorialH ypertension continues to be a significant worldwide health challenge contributing to the rates of morbidity and mortality related to heart failure, ischemic stroke, renal disease, atherosclerosis, and cardiac hypertrophy. Contributions to hypertension include multiple organs including the kidneys, peripheral vasculature, and the central and autonomic nervous systems. One of the most recent advances in our understanding of underlying factors that influence the development and prevalence of hypertension is the role of the inflammation and the immune system. 2 The role of T cells in the development of hypertension has been demonstrated in number of studies, 3,4 and both hypertensive humans and male animals models of hypertension have shown T-cell accumulation in the kidneys and vasculature.5-7 Furthermore, T cells have been shown to be required for the development of some forms of hypertension. In initial studies using the angiotensin II (Ang II) infusion model of hypertension and a male mouse model lacking lymphocytes because of a deficiency in the recombination activating gene (Rag-1 −/− ), when these mice were infused with Ang II, the level of hypertension was significantly less than that observed in wild-type male mice. 8 When the T cells from a male wild-type donor were given back to the male Rag-1 −/− mice, the hypertensive effects of Ang II were restored, suggesting that Ang II-induced hypertension requires the adaptive immune system and T cells in particular. It should be noted, however, that this effect of T cells to induce hypertension is not present in female animal models 7 and requires using T cells from male donors, 6 suggesting that there are clear sex differences in the role of the immune system in hypertension. Article, see p 858A recent study by Shah et al 9 aimed at further exposing the role of the immune system and inflammation in the development of hypertension focused on the role of myeloid-derived suppressor cells (MDSCs). The MDSCs are a heterogeneous population of immature myeloid cells that are known to suppress the effects of the adaptive immune system and T-cell responses in particular.10,11 The role of MDSCs in suppressing inflammation-related diseases has a been demonstrated in patients with cancer, 12 autoimmune disease, 13 as well as chronic infection and inflammatory bowel disease.14 Given what we know now about the role of inflammation and T cells in the development of hypertension, this new study offers important and timely insight for the role of MDSCs in the development of hypertension.The study by Shah et al 9 offers a comprehensive and through examination of the effect of MDSCs in 3 different forms of hypertension including Ang II infusion induced hypertension, hypertension induced by giving mice l-n-nitroarginine methyl ester (L-NAME) supplements and also a high-salt model of hypertension. Importantly, all of the mice used in the study were male and so the results can only be extrapolated to the role of MDSCs in males. The authors measured the numbers of peripheral...

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Myeloid-Derived Suppressor Cells

Cited by 429 publications

References 194 publications

Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function

Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function

Immature myeloid cells in the tumor microenvironment: Implications for immunotherapy

The Good and the Bad

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