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Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy

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Abstract

Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response. Myeloid-derived suppressor cells (MDSC) contribute to cancerogenesis by forming a favorable microenvironment for tumor growth. Proinflammatory cytokines, secreted by tumor cells and the tumor microenvironment, induce angiogenesis and metastasis and promote tumor growth. They also provide signals necessary for survival, accumulation, and function of MDSC. Understanding the mechanisms of myeloid suppressor cell development and the use of proinflammatory cytokine inhibitors may prove beneficial for tumor therapy.

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Abbreviations

Arg1:

arginase 1

G-CSF:

granulocyte colonystimulating factor

GM-CSF:

granulocyte-macrophage colony-stimulating factor

IDO:

indolamine-2,3-dioxygenase

IL:

interleukin

iNOS:

inducible NO-synthase

M-CSF:

monocyte-macrophage colony-stimulating factor

MDSC:

myeloid-derived suppressor cells

ROS:

reactive oxygen species

sTNF:

soluble form of TNF

TCR:

T-cell receptor

TGF-ß:

transforming growth factor beta

tmTNF:

transmembrane TNF

TNF:

tumor necrosis factor

TNFR:

tumor necrosis factor receptor

Treg:

regulatory T cells

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, 119991, Moscow, Russia

    K.-S. N. Atretkhany & M. S. Drutskaya

  2. Biological Faculty, Lomonosov Moscow State University, 119991, Moscow, Russia

    K.-S. N. Atretkhany & M. S. Drutskaya

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  1. K.-S. N. Atretkhany
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  2. M. S. Drutskaya
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Correspondence to M. S. Drutskaya.

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Published in Russian in Biokhimiya, 2016, Vol. 81, No. 11, pp. 1520–1529.

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Atretkhany, KS.N., Drutskaya, M.S. Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy. Biochemistry Moscow 81, 1274–1283 (2016). https://doi.org/10.1134/S0006297916110055

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