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How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions

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Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of mononuclear and polymorphonuclear myeloid cells, which are present at very low numbers in healthy subjects, but can expand substantially under disease conditions. Depending on disease type and stage, MDSC comprise varying amounts of immature and mature differentiation stages of myeloid cells. Validated unique phenotypic markers for MDSC are still lacking. Therefore, the functional analysis of these cells is of central importance for their identification and characterization. Various disease-promoting and immunosuppressive functions of MDSC are reported in the literature. Among those, the capacity to modulate the activity of T cells is by far the most often used and best-established read-out system. In this review, we critically evaluate the assays available for the functional analysis of human and murine MDSC under in vitro and in vivo conditions. We also discuss critical issues and controls associated with those assays. We aim at providing suggestions and recommendations useful for the contemporary biological characterization of MDSC.

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Abbreviations

ATRA:

All-trans retinoic acid

Arg1, ARG1, ARG1:

Arginase-1

BrdU:

Bromodeoxyuridine

CFSE:

Carboxyfluorescein succinimidyl ester

COST:

European Cooperation in Science and Technology

DCFDA:

2′,7′-dichlorofluorescin diacetate

EU:

European Union

KO:

Knock-out

M:

Monocytic

MDSC:

Myeloid-derived suppressor cell(s)

Nos2, NOS2, NOS2:

(inducible) nitric oxide synthase 2

PMN:

Polymorphonuclear

ROS:

Reactive oxygen species

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Acknowledgements

We thank all members of Mye-EUNITER for contributions and discussions during the preparation of this manuscript. We also thank all members of the Esendagli laboratory at Hacettepe University Cancer Institute for their help with the quantitative and qualitative analysis of the literature.

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.

Author information

Authors and Affiliations

  1. de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, 1200, Brussels, Belgium

    Annika M. Bruger & Pierre van der Bruggen

  2. Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany and Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany

    Anca Dorhoi

  3. Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

    Gunes Esendagli

  4. Institute of Immunology, University of Münster, Münster, Germany

    Katarzyna Barczyk-Kahlert

  5. Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics AS CR, Videnska 1083, 142 20, Prague 4, Czech Republic

    Marie Lipoldova

  6. Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, 841 04, Bratislava, Slovak Republic

    Tomas Perecko

  7. Molecular Oncology group, Institute for Medical Research, University of Belgrade, Belgrade, Republic of Serbia

    Juan Santibanez

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

    Juan Santibanez

  9. Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal

    Margarida Saraiva

  10. Instituto de Biologia Molecular e Celular, University of Porto, Porto, Portugal

    Margarida Saraiva

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

    Jo A. Van Ginderachter

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

    Jo A. Van Ginderachter

  13. Research Division, Department of Otorhinolaryngology, West German Cancer Center, University Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany

    Sven Brandau

Authors
  1. Annika M. Bruger
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  2. Anca Dorhoi
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  3. Gunes Esendagli
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  4. Katarzyna Barczyk-Kahlert
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  5. Pierre van der Bruggen
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  6. Marie Lipoldova
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  7. Tomas Perecko
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  8. Juan Santibanez
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  9. Margarida Saraiva
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  10. Jo A. Van Ginderachter
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  11. Sven Brandau
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Contributions

AMB and SB conceptualized the review. All authors contributed to the writing and editing of the review. All authors approved the final version.

Corresponding author

Correspondence to Sven Brandau.

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Conflict of interest

The authors declare no conflict of interest.

Additional information

Jo A. Van Ginderachter and Sven Brandau co-senior authors.

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), funded by the COST programme of the European Union (http://www.mye-euniter.eu).

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Bruger, A.M., Dorhoi, A., Esendagli, G. et al. How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions. Cancer Immunol Immunother 68, 631–644 (2019). https://doi.org/10.1007/s00262-018-2170-8

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  • DOI: https://doi.org/10.1007/s00262-018-2170-8

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