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Myeloid-Derived Suppressor Cells (MDSCs) in Haematology
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Myeloid-Derived Suppressor Cells (MDSCs) in Haematology

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (10 July 2022) | Viewed by 35012

Special Issue Editor

Prof. Dr. Helen A. Papadaki

E-Mail Website
Guest Editor
1. Hemopoiesis Research Laboratory, School of Medicine, University of Crete, 71500 Heraklion, Greece
2. Department of Hematology, University Hospital of Heraklion, 71500 Heraklion, Greece
Interests: neutropenia; bone marrow failure; clonal hematopoiesis; myeloid derived suppressor cells; umbilical cord blood

Special Issue Information

Dear Colleagues,

It is my honor to serve as the Guest Editor of the Special Issue “Myeloid-Derived Suppressor Cells (MDSCs) in Haematology” of the Journal of Clinical Medicine, and I would like to invite you to submit a relevant review and/or paper with new data from your research in the field. This issue will serve as a great opportunity to highlight the role of MDSCs in the pathophysiology of immune-mediated and malignant haematologic diseases and how research in the field may advance the clinical practice, particularly in the context of precision medicine.

MDSCs are immature myeloid cells with immunomodulating properties, mainly acting by suppressing T-cell responses. Most experimental and clinical studies concerning MDSCs have been focused on solid tumors, as these cells contribute to malignant cell expansion, local angiogenesis, and drug resistance. In recent years, however, the implication of MDSCs in the immune dysregulation associated with haematologic malignancies, immune-mediated cytopenias, and allogeneic haemopoietic stem cell transplantation has been documented; thus, the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in haematology. There is already evidence that MDSCs display altered frequency and/or functionality and could be targeted in myelodysplastic syndromes, lymphomas, myeloproliferative neoplasms, leukemia, multiple myeloma, immune mediated cytopenias, and graft-versus-host disease. The better understanding of the quantitative/functional properties of MDSCs and the mechanisms of their crosstalk with other regulatory (e.g., T-cells, natural killer cells, mesenchymal stem cells) and malignant cells in haematologic diseases may facilitate the development of novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation of MDSCs) and the recognition of novel biomarkers for personalized treatment approaches. Thus, the issue aims to cover this broad spectrum.

I look forward to receiving your submissions.

Prof. Dr. Helen A. Papadaki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Myeloid-derived suppressor cells (MDSCs)
  • Hematologic malignancies
  • Immune-mediated cytopenias
  • Graft-versus-host disease
  • Therapeutic target
  • Biomarker
  • Precision medicine
  • Immunosuppression
  • Molecular pathways
  • Bone marrow microenvironment

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 189 KiB  
Editorial
Myeloid-Derived Suppressor Cells (MDSCs) in Haematology
by Nikoleta Bizymi and Helen A. Papadaki
J. Clin. Med. 2022, 11(1), 187; https://doi.org/10.3390/jcm11010187 - 30 Dec 2021
Cited by 3 | Viewed by 1543
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunomodulating properties, mainly acting by suppressing T-cell responses [...] Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)

Research

Jump to: Editorial, Review

11 pages, 2144 KiB  
Article
Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients
by Zhitao Wang, Rui Jiang, Qian Li, Huiping Wang, Qianshan Tao and Zhimin Zhai
J. Clin. Med. 2021, 10(8), 1768; https://doi.org/10.3390/jcm10081768 - 19 Apr 2021
Cited by 17 | Viewed by 2284
Abstract
Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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Review

Jump to: Editorial, Research

23 pages, 1079 KiB  
Review
New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology
by Nikoleta Bizymi, Andreas M. Matthaiou, Angelos Matheakakis, Ioanna Voulgari, Nikoletta Aresti, Konstantina Zavitsanou, Anastasios Karasachinidis, Irene Mavroudi, Charalampos Pontikoglou and Helen A. Papadaki
J. Clin. Med. 2022, 11(18), 5326; https://doi.org/10.3390/jcm11185326 - 10 Sep 2022
Cited by 10 | Viewed by 2941
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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15 pages, 604 KiB  
Review
Myeloid-Derived Suppressor Cells: New Insights into the Pathogenesis and Therapy of MDS
by Maria Velegraki, Andrew Stiff, Helen A. Papadaki and Zihai Li
J. Clin. Med. 2022, 11(16), 4908; https://doi.org/10.3390/jcm11164908 - 21 Aug 2022
Cited by 6 | Viewed by 3614
Abstract
Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by the clonal expansion of hematopoietic stem cells, bone marrow failure manifested by cytopenias, and increased risk for evolving to acute myeloid leukemia. Despite the fact that the acquisition of somatic mutations is considered key for [...] Read more.
Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by the clonal expansion of hematopoietic stem cells, bone marrow failure manifested by cytopenias, and increased risk for evolving to acute myeloid leukemia. Despite the fact that the acquisition of somatic mutations is considered key for the initiation of the disease, the bone marrow microenvironment also plays significant roles in MDS by providing the right niche and even shaping the malignant clone. Aberrant immune responses are frequent in MDS and are implicated in many aspects of MDS pathogenesis. Recently, myeloid-derived suppressor cells (MDSCs) have gained attention for their possible implication in the immune dysregulation associated with MDS. Here, we summarize the key findings regarding the expansion of MDSCs in MDS, their role in MDS pathogenesis and immune dysregulation, as well their potential as a new therapeutic target for MDS. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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20 pages, 791 KiB  
Review
Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies
by Iosif Papafragkos, Efrosyni Markaki, Christina Kalpadakis and Panayotis Verginis
J. Clin. Med. 2021, 10(16), 3462; https://doi.org/10.3390/jcm10163462 - 4 Aug 2021
Cited by 9 | Viewed by 3047
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid precursors which emerged as a potent regulator of the immune system, exerting suppressive properties in diverse disease settings. In regards to cancer, MDSCs have an established role in solid tumors; however, their contribution to immune regulation [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are immature myeloid precursors which emerged as a potent regulator of the immune system, exerting suppressive properties in diverse disease settings. In regards to cancer, MDSCs have an established role in solid tumors; however, their contribution to immune regulation during hematologic malignancies and particularly in lymphomas remains ill-defined. Herein focused on lymphoma, we discuss the literature on MDSC cells in all histologic types, and we also refer to lessons learned by animal models of lymphoma. Furthermore, we elaborate on future directions and unmet needs and challenges in the MDSC field related to lymphoma malignancies which may shed light on the complex nature of the immune system in malignancies. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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20 pages, 3439 KiB  
Review
MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer
by Christophe Vanhaver, Pierre van der Bruggen and Annika M. Bruger
J. Clin. Med. 2021, 10(13), 2872; https://doi.org/10.3390/jcm10132872 - 28 Jun 2021
Cited by 45 | Viewed by 8010
Abstract
Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs’ rarity, short lifespan, heterogeneity, poor viability after freezing and the lack [...] Read more.
Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs’ rarity, short lifespan, heterogeneity, poor viability after freezing and the lack of MDSC-specific markers. In this review, we will compare identification and isolation strategies for human and murine MDSCs. We will also assess what direct and indirect immunosuppressive mechanisms have been attributed to MDSCs. While some immunosuppressive mechanisms are well-documented in mice, e.g., generation of ROS, direct evidence is still lacking in humans. In future, bulk or single-cell genomics could elucidate which phenotypic and functional phenotypes MDSCs adopt in particular microenvironments and help to identify potential targets for therapy. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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26 pages, 1081 KiB  
Review
Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies
by Suncica Kapor and Juan F. Santibanez
J. Clin. Med. 2021, 10(13), 2788; https://doi.org/10.3390/jcm10132788 - 24 Jun 2021
Cited by 20 | Viewed by 4430
Abstract
Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone [...] Read more.
Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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16 pages, 781 KiB  
Review
The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD)
by Christos Demosthenous, Ioanna Sakellari, Vassiliki Douka, Penelope Georgia Papayanni, Achilles Anagnostopoulos and Eleni Gavriilaki
J. Clin. Med. 2021, 10(10), 2050; https://doi.org/10.3390/jcm10102050 - 11 May 2021
Cited by 24 | Viewed by 3479
Abstract
Background: Myeloid-derived suppressor cells (MDSCs) are implicated in the complex interplay involving graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT) in hematologic malignancies. Methods: A review of literature through PubMed was undertaken to summarize the published evidence [...] Read more.
Background: Myeloid-derived suppressor cells (MDSCs) are implicated in the complex interplay involving graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT) in hematologic malignancies. Methods: A review of literature through PubMed was undertaken to summarize the published evidence on the pathophysiology and clinical implications of MDSCs in allo-HCT. Literature sources published in English since 1978 were searched, using the terms Natural Suppressor (NS) cells, MDSCs, GVHD, and allo-HCT. Results: In vivo studies demonstrated that MDSCs derived from mobilization protocols could strongly suppress allo-responses mediated by T cells and enhance T-Reg activity, thus inhibiting GVHD toxicity. However, the influence of MDSCs on the GVL effect is not fully defined. Conclusions: The induction or maintenance of MDSC suppressive function would be advantageous in suppressing inflammation associated with GVHD. Pathways involved in MDSC metabolism and the inflammasome signaling are a promising field of study to elucidate the function of MDSCs in the pathogenesis of GVHD and translate these findings to a clinical setting. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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21 pages, 1287 KiB  
Review
Resistance to Immune Checkpoint Inhibitors Secondary to Myeloid-Derived Suppressor Cells: A New Therapeutic Targeting of Haematological Malignancies
by Alejandro Olivares-Hernández, Luis Figuero-Pérez, Eduardo Terán-Brage, Álvaro López-Gutiérrez, Álvaro Tamayo Velasco, Rogelio González Sarmiento, Juan Jesús Cruz-Hernández and José Pablo Miramontes-González
J. Clin. Med. 2021, 10(9), 1919; https://doi.org/10.3390/jcm10091919 - 28 Apr 2021
Cited by 5 | Viewed by 2366
Abstract
Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are a set of immature myeloid lineage cells that include macrophages, granulocytes, and dendritic cell precursors. This subpopulation has been described in relation to the tumour processes at different levels, including resistance to immunotherapy, such as immune checkpoint inhibitors (ICIs). Currently, multiple studies at the preclinical and clinical levels seek to use this cell population for the treatment of different haematological neoplasms, together with ICIs. This review addresses the different points in ongoing studies of MDSCs and ICIs in haematological malignancies and their future significance in routine clinical practice. Full article
(This article belongs to the Special Issue Myeloid-Derived Suppressor Cells (MDSCs) in Haematology)
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