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Cancer Immunology, Immunotherapy

, Volume 68, Issue 4, pp 645–660 | Cite as

Interactions among myeloid regulatory cells in cancer

  • Viktor UmanskyEmail author
  • Gosse J. Adema
  • Jaroslaw Baran
  • Sven Brandau
  • Jo A. Van Ginderachter
  • Xiaoying Hu
  • Jadwiga Jablonska
  • Slavko Mojsilovic
  • Helen A. Papadaki
  • Yago Pico de Coaña
  • Kim C. M. Santegoets
  • Juan F. Santibanez
  • Karine Serre
  • Yu Si
  • Isabela Sieminska
  • Maria Velegraki
  • Zvi G. Fridlender
Symposium-in-Writing Paper

Abstract

Mounting evidence has accumulated on the critical role of the different myeloid cells in the regulation of the cancerous process, and in particular in the modulation of the immune reaction to cancer. Myeloid cells are a major component of host cells infiltrating tumors, interacting with each other, with tumor cells and other stromal cells, and demonstrating a prominent plasticity. We describe here various myeloid regulatory cells (MRCs) in mice and human as well as their relevant therapeutic targets. We first address the role of the monocytes and macrophages that can contribute to angiogenesis, immunosuppression and metastatic dissemination. Next, we discuss the differential role of neutrophil subsets in tumor development, enhancing the dual and sometimes contradicting role of these cells. A heterogeneous population of immature myeloid cells, MDSCs, was shown to be generated and accumulated during tumor progression as well as to be an important player in cancer-related immune suppression. Lastly, we discuss the role of myeloid DCs, which can either contribute to effective anti-tumor responses or play a more regulatory role. We believe that MRCs play a critical role in cancer-related immune regulation and suggest that future anti-cancer therapies will focus on these abundant cells.

Keywords

Myeloid regulatory cells Mye-EUNITER Macrophages Neutrophils Myeloid-derived suppressor cells Dendritic cells 

Abbreviations

Arg

Arginase

CCL

C–C motif ligand

cDC

Classical dendritic cell

CXCL

C–X–C motif ligand

DCs

Dendritic cells

EBV

Epstein–Barr virus

EGF

Epidermal growth factor

FGF

Fibroblast growth factor

HDNs

High-density neutrophils

HGF

Hepatocyte growth factor

iNOS

Inducible NO synthase

LDNs

Low-density neutrophils

LFA

Lymphocyte function-associated antigen

Mac

Macrophage antigen

M-CSF

Macrophage colony-stimulating factor

M-MDSCs

Monocytic MDSCs

MMPs

Matrix metalloproteinases

MRCs

Myeloid regulatory cells

NLR

Neutrophil to lymphocyte ratio

PDGF

Platelet-derived growth factor

PLGF

Placenta growth factor

PMN-MDSCs

Polymorphonuclear MDSCs

TAMs

Tumor-associated macrophages

TANs

Tumor-associated neutrophils

TGF

Transforming growth factor

Notes

Author contributions

VU, ZGF: writing and revision of the manuscript, revision of the tables and figures. GA, JB, SB, JAVG, JJ, HAP, KCMS, JFS, KS, MV: writing and revision of the manuscript and preparation of the tables. YPC, IS: preparation of the figures. XH, SM, YS: revision of the manuscript and figures.

Funding

This work was supported by COST (European Cooperation in Science and Technology) and the COST Action BM1404 Mye-EUNITER (http://www.mye-euniter.eu). COST is part of the EU Framework Programme Horizon 2020. This work was also supported by Grants from the Cooperation between German Cancer Research Center (DKFZ) and Ministry of Science, Technology and Space of Israel (MOST) in Cancer Research (CA181 to V. Umansky and Z.G. Fridlender).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Viktor Umansky
    • 1
    • 2
    Email author
  • Gosse J. Adema
    • 3
  • Jaroslaw Baran
    • 4
  • Sven Brandau
    • 5
  • Jo A. Van Ginderachter
    • 6
    • 7
  • Xiaoying Hu
    • 1
    • 2
  • Jadwiga Jablonska
    • 5
  • Slavko Mojsilovic
    • 8
  • Helen A. Papadaki
    • 9
  • Yago Pico de Coaña
    • 10
  • Kim C. M. Santegoets
    • 3
  • Juan F. Santibanez
    • 11
    • 12
  • Karine Serre
    • 13
  • Yu Si
    • 5
  • Isabela Sieminska
    • 4
  • Maria Velegraki
    • 9
  • Zvi G. Fridlender
    • 14
  1. 1.Skin Cancer Unit (G300)German Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Dermatology, Venereology and Allergology, University Medical Center MannheimRuprecht Karl University of HeidelbergMannheimGermany
  3. 3.Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical CenterRadboud Institute for Molecular Life SciencesNijmegenThe Netherlands
  4. 4.Department of Clinical Immunology, Institute of PaediatricsJagiellonian University Medical CollegeKrakówPoland
  5. 5.Department of Otorhinolaryngology, University Hospital EssenUniversity Duisburg-EssenEssenGermany
  6. 6.Lab of Cellular and Molecular ImmunologyVrije Universiteit BrusselBrusselsBelgium
  7. 7.Myeloid Cell Immunology LabVIB Center for Inflammation ResearchBrusselsBelgium
  8. 8.Laboratory for Experimental Hematology and Stem Cells, Institute for Medical ResearchUniversity of BelgradeBelgradeRepublic of Serbia
  9. 9.Department of Hematology, School of MedicineUniversity of CreteHeraklionGreece
  10. 10.Department of Oncology and PathologyKarolinska InstitutetStockholmSweden
  11. 11.Department of Molecular Oncology, Institute for Medical ResearchUniversity of BelgradeBelgradeRepublic of Serbia
  12. 12.Centro Integrativo de Biología y Química Aplicada (CIBQA)Universidad Bernardo O’HigginsSantiagoChile
  13. 13.Faculty of Medicine, Institute of Molecular Medicine (IMM)-João Lobo AntunesUniversity of LisbonLisbonPortugal
  14. 14.Institute of Pulmonary MedicineHadassah-Hebrew University Medical CenterJerusalemIsrael

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