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Review
. 2022 Sep 10;11(18):5326.
doi: 10.3390/jcm11185326.

New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology

Nikoleta Bizymi  1   2   3 , Andreas M Matthaiou  3   4 , Angelos Matheakakis  1   2 , Ioanna Voulgari  1   2 , Nikoletta Aresti  1   2 , Konstantina Zavitsanou  1   2 , Anastasios Karasachinidis  1   2 , Irene Mavroudi  1   2 , Charalampos Pontikoglou  1   2 , Helen A Papadaki  1   2
Affiliations
Review

New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology

Nikoleta Bizymi et al. J Clin Med. .

Abstract

Myeloid-derived suppressor cells (MDSCs) are immature cells of myeloid origin that have gained researchers' attention, as they constitute promising biomarkers and targets for novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation) in several conditions, including neoplastic, autoimmune, infective, and inflammatory diseases, as well as pregnancy, obesity, and graft rejection. They are characterised in humans by the typical immunophenotype of CD11b+CD33+HLA-DR-/low and immune-modulating properties leading to decreased T-cell proliferation, induction of T-regulatory cells (T-regs), hindering of natural killer (NK) cell functionality, and macrophage M2-polarisation. The research in the field is challenging, as there are still difficulties in defining cell-surface markers and gating strategies that uniquely identify the different populations of MDSCs, and the currently available functional assays are highly demanding. There is evidence that MDSCs display altered frequency and/or functionality and could be targeted in immune-mediated and malignant haematologic diseases, although there is a large variability of techniques and results between different laboratories. This review presents the current literature concerning MDSCs in a clinical point of view in an attempt to trigger future investigation by serving as a guide to the clinical haematologist in order to apply them in the context of precision medicine as well as the researcher in the field of experimental haematology.

Keywords: autoimmunity; biomarker; cancer; haematology; immune dysregulation; immunology; immunotherapy; infection; inflammation; myeloid-derived suppressor cell (MDSC).

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Conflict of interest statement

The authors declare no conflict of interest. The funders (Janssen Research and Development LLC) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Theories of the origin of MDSCs. The classical theory of the generation of MDSCs is the “two-signal model”. The HSC under the effect of GFs becomes IMC, which under the effect of PIFs turns into an activated with suppressive character cell, i.e., MDSC. Besides the bone marrow, there are also other sites of generation of these cells such as at the site of the tumour, in the spleen, and in the placenta and umbilical cord. Another theory is the reprogramming under specific triggers of mature neutrophils and monocytes to PMN-MDSCs and M-MDSCs, respectively. Abbreviations: HSC—haematopoietic stem cell; IMC—immature myeloid cell; GF—growth factors; PIF—pro-inflammatory factors; MDSC—myeloid-derived suppressor cell; PMN-MDSC—polymorphonuclear-MDSC; M-MDSC—monocytic-MDSC.
Figure 2
Figure 2
Mechanisms of action of MDSCs. MDSCs are thought to be cells with immune-modulatory properties. These cells are thought to be elevated and play an important role in chronic inflammation, tumour progression, and immunosenescence. They act through several mechanisms such as inhibition of T-cell responses, induction of T-regs, M2 macrophage polarisation, etc. However, they have also beneficial roles such as in foetal–maternal tolerance and during infant infections. Abbreviations: MDSCs—myeloid-derived suppressor cells; T-regs—T regulatory cells.
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