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Interactions among myeloid regulatory cells in cancer

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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.

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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

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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).

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Authors and Affiliations

  1. Skin Cancer Unit (G300), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Viktor Umansky & Xiaoying Hu

  2. Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht Karl University of Heidelberg, Mannheim, Germany

    Viktor Umansky & Xiaoying Hu

  3. Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands

    Gosse J. Adema & Kim C. M. Santegoets

  4. Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Kraków, Poland

    Jaroslaw Baran & Isabela Sieminska

  5. Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Essen, Germany

    Sven Brandau, Jadwiga Jablonska & Yu Si

  6. Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium

    Jo A. Van Ginderachter

  7. Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium

    Jo A. Van Ginderachter

  8. Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Republic of Serbia

    Slavko Mojsilovic

  9. Department of Hematology, School of Medicine, University of Crete, Heraklion, Greece

    Helen A. Papadaki & Maria Velegraki

  10. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden

    Yago Pico de Coaña

  11. Department of Molecular Oncology, Institute for Medical Research, University of Belgrade, Belgrade, Republic of Serbia

    Juan F. Santibanez

  12. Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago, Chile

    Juan F. Santibanez

  13. Faculty of Medicine, Institute of Molecular Medicine (IMM)-João Lobo Antunes, University of Lisbon, Lisbon, Portugal

    Karine Serre

  14. Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Zvi G. Fridlender

Authors
  1. Viktor Umansky
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  2. Gosse J. Adema
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  3. Jaroslaw Baran
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  6. Xiaoying Hu
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  14. Yu Si
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  17. Zvi G. Fridlender
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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.

Corresponding author

Correspondence to Viktor Umansky.

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The authors declare no conflict of interest.

Additional information

This paper is part of a Symposium-in-Writing in Cancer Immunology, Immunotherapy by members of the European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells (Mye-EUNITER network).

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Umansky, V., Adema, G.J., Baran, J. et al. Interactions among myeloid regulatory cells in cancer. Cancer Immunol Immunother 68, 645–660 (2019). https://doi.org/10.1007/s00262-018-2200-6

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