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Cancer Microenvironment

, Volume 6, Issue 2, pp 169–177 | Cite as

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

  • Viktor Umansky
  • Alexandra Sevko
Original Paper

Abstract

Tumor progression has been demonstrated to be supported by chronic inflammatory conditions developed in the tumor microenvironment and characterized by the long-term secretion of various inflammatory soluble factors (including cytokines, chemokines, growth factors, reactive oxygen and nitrogen species, prostaglandins etc.) and strong leukocyte infiltration. Among leukocytes infiltrating tumors, myeloid-derived suppressor cells (MDSCs) represent one of the most important players mediating immunosuppression. These cells may not only strongly inhibit an anti-tumor immune reactions mediated by T cells but also directly stimulate tumorigenesis, tumor growth and metastasis by enhancing neoangiogenesis and creating a suitable environment for the metastatic formation. This review provides an overview of interactions between MDSCs and tumor cells leading to MDSC generation, activation and migration to the tumor site, where they can strongly enhance tumor progression. Better understanding of the MDSC-tumor interplay is critical for the development of new strategies of tumor immunotherapy.

Keywords

Myeloid-derived suppressor cells Cancer Immunosuppression Tumor microenvironment Chronic inflammatory factors Tumorigenesis 

Abbreviations

MDSCs

myeloid-derived suppressor cells

VEGF

vascular endothelial growth factor

TGF

transforming growth factor

IL

interleukin

Tregs

regulatory T cells

TAMs

tumor-associated macrophages

DCs

dendritic cells

STAT

signal transducer and activator of transcription

iNOS

inducible nitric oxide synthase

ARG

arginase

NO

nitric oxide

ROS

reactive oxygen species

TCR

T cell receptor

TNF

tumor necrosis factor

IFN

interferon

GM-CSF

granulocyte-macrophage colony-stimulating factor

G-CSF

granulocyte colony-stimulating factor

M-CSF

macrophage colony-stimulating factor

CCL

chemokine C-C motif ligand

COX

cyclooxygenase

PGE2

prostaglandin E2

SCF

stem cell factor

ATRA

all-trans-retinoic acid

Notes

Acknowledgments

This work was supported by the DKFZ-MOST Cooperation in Cancer Research (grant CA128, to VU), Dr. Mildred Scheel Foundation for Cancer Research (grant 108992, to VU), the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Immunotherapy of Cancer (to VU).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Skin Cancer Unit, German Cancer Research CenterHeidelbergGermany
  2. 2.Department of Dermatology, Venereology and Allergology, University Medical Center MannheimRuprecht-Karl University of HeidelbergHeidelbergGermany

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