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

  • Annika M. Bruger
  • Anca Dorhoi
  • Gunes Esendagli
  • Katarzyna Barczyk-Kahlert
  • Pierre van der Bruggen
  • Marie Lipoldova
  • Tomas Perecko
  • Juan Santibanez
  • Margarida Saraiva
  • Jo A. Van Ginderachter
  • Sven Brandau
Symposium-in-Writing Paper
  • 402 Downloads

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.

Keywords

Myeloid-derived suppressor cells T cells Immunosuppression Arginase Proliferation Mye-EUNITER 

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

Notes

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.

Author contributions

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

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.

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

  • Annika M. Bruger
    • 1
  • Anca Dorhoi
    • 2
  • Gunes Esendagli
    • 3
  • Katarzyna Barczyk-Kahlert
    • 4
  • Pierre van der Bruggen
    • 1
  • Marie Lipoldova
    • 5
  • Tomas Perecko
    • 6
  • Juan Santibanez
    • 7
    • 8
  • Margarida Saraiva
    • 9
    • 10
  • Jo A. Van Ginderachter
    • 11
    • 12
  • Sven Brandau
    • 13
  1. 1.de Duve InstituteUniversité catholique de LouvainBrusselsBelgium
  2. 2.Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany and Faculty of Mathematics and Natural SciencesUniversity of GreifswaldGreifswaldGermany
  3. 3.Department of Basic OncologyHacettepe University Cancer InstituteAnkaraTurkey
  4. 4.Institute of ImmunologyUniversity of MünsterMünsterGermany
  5. 5.Laboratory of Molecular and Cellular ImmunologyInstitute of Molecular Genetics AS CRPrague 4Czech Republic
  6. 6.Institute of Experimental Pharmacology and ToxicologySlovak Academy of SciencesBratislavaSlovak Republic
  7. 7.Molecular Oncology group, Institute for Medical ResearchUniversity of BelgradeBelgradeRepublic of Serbia
  8. 8.Centro Integrativo de Biología y Química Aplicada (CIBQA)Universidad Bernardo O’HigginsSantiagoChile
  9. 9.Instituto de Investigação e Inovação em SaúdeUniversity of PortoPortoPortugal
  10. 10.Instituto de Biologia Molecular e CelularUniversity of PortoPortoPortugal
  11. 11.Cellular and Molecular Immunology LabVrije Universiteit BrusselBrusselsBelgium
  12. 12.Myeloid Cell Immunology LabVIB Center for Inflammation ResearchBrusselsBelgium
  13. 13.Research Division, Department of OtorhinolaryngologyWest German Cancer Center, University Hospital EssenEssenGermany

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