Special Issue "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: 10 July 2022.

Special Issue Editor

Prof. Dr. Helen A. Papadaki
E-Mail Website
Guest Editor
Haemopoiesis Research Laboratory, School of Medicine, University of Crete and Department of Haematology, University Hospital of Heraklion, PO Box 1352, 71500 Heraklion, Crete, Greece
Interests: hematology; chronic neutropenia; bone marrow failure syndromes; myeloid derived suppressor cells; mesenchymal stem cells; umbilical cord blood; precision medicine

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 papers will be 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.

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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

Published Papers (7 papers)

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Editorial

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Editorial
Myeloid-Derived Suppressor Cells (MDSCs) in Haematology
J. Clin. Med. 2022, 11(1), 187; https://doi.org/10.3390/jcm11010187 - 30 Dec 2021
Viewed by 163
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

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Article
Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients
J. Clin. Med. 2021, 10(8), 1768; https://doi.org/10.3390/jcm10081768 - 19 Apr 2021
Cited by 5 | Viewed by 628
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

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Review
Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies
J. Clin. Med. 2021, 10(16), 3462; https://doi.org/10.3390/jcm10163462 - 04 Aug 2021
Cited by 2 | Viewed by 733
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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Review
MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer
J. Clin. Med. 2021, 10(13), 2872; https://doi.org/10.3390/jcm10132872 - 28 Jun 2021
Cited by 4 | Viewed by 1035
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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Review
Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies
J. Clin. Med. 2021, 10(13), 2788; https://doi.org/10.3390/jcm10132788 - 24 Jun 2021
Cited by 3 | Viewed by 672
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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Review
The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD)
J. Clin. Med. 2021, 10(10), 2050; https://doi.org/10.3390/jcm10102050 - 11 May 2021
Cited by 2 | Viewed by 1040
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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Review
Resistance to Immune Checkpoint Inhibitors Secondary to Myeloid-Derived Suppressor Cells: A New Therapeutic Targeting of Haematological Malignancies
J. Clin. Med. 2021, 10(9), 1919; https://doi.org/10.3390/jcm10091919 - 28 Apr 2021
Cited by 3 | Viewed by 647
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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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. New perspectives on Myeloid-Derived Suppressor Cells (MDSCs) and their emerging role in Haematology

(Abstract: Human Myeloid-Derived Suppressor Cells (MDSCs) are immature myeloid cells, characterized as CD11b+CD33+HLA-DR–/low cells that have immuno-modulating properties. They display altered frequency and functionality and may serve as promising biomarkers and targets for novel therapeutic strategies in several conditions, involving immune-mediated and malignant haematologic diseases. However, there are still difficulties in defining cell-surface markers that uniquely identify them and the functional assays are demanding. This review will try to present the current literature in a clinical point of view and trigger future investigation by serving as a guide to the clinical haematologist as well as the researcher in the field of experimental haematology.)

2. Myeloid-derived Suppressor Cell (MDSC) subsets in the Umbilical Blood Cord (UBC)

(Abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that suppresses immune responses in cancer, infection and trauma, associated with poor prognosis. However, they may play a positive role in allogeneic haematopoietic stem cell transplantation inhibiting Graft-versus-Host Disease. Moreover, they are beneficial during pregnancy, as increased numbers of MDSCs, and especially granulocytic MDSCs, are crucial in immunological tolerance between mother and fetus and in the fetus growth process. Thus, human umbilical cord blood is a source rich in MDSCs. Several pregnancy complications are due to their dysregulation. The current review summarizes their roles and applications in the umbilical cord blood.)

3. Myelodysplastic Syndromes

4. Myeloproliferative Neoplasms

5. Mesenchymal Stromal Cells and Myeloid-derived suppressor cells interaction: an immunoregulatory partnership in hematologic diseases?

(Abstract: Mesenchymal stromal cells (MSCs) and myeloid-derived suppressor cells (MDSC) display immunoregulatory properties by controlling the innate and adaptive immune system that may induce a tolerant and supportive microenvironment for cancer development. So far, the interaction of MSC and MDSC into the cancer microenvironment remains a subject to be elucidated and understood. In this review, we will analyse the mutual contribution of both MSC and MDSC on the production of a tolerant cancer microenvironment, including the immunosuppressive similarities with main emphasis on haematologic diseases and their potential use in combined therapeutic strategies.)

6. Arginine deprivation can predict clinical outcome in Hodgkin Lymphoma

7. Graft-versus-Host Disease

8. MDSCs role in T-cell Lymphomas

9. Resistance to immune checkpoint inhibitors secondary to myeloid-derived suppressor cells: a new therapeutic targeting of haematologic diseases

10. MDSC in mice and men: mechanisms of immunosuppression

(Abstract: In this review, we will compare the latest insights into the immunosuppressive mechanisms murine and human myeloid-derived suppressor cells (MDSC) employ. Studying MDSC immunosuppression is hampered by their rarity, short life-spans, heterogeneity and poor viability after freezing. In mouse models, genetic manipulations can pinpoint the effect of particular enzymes or cytokines. In contrast, human studies principally rely on samples obtained from patient blood and are limited to simpler suppression assays, e.g. T cell proliferation. Therefore, some well-documented immunosuppressive mechanisms reported in mice, e.g. via immune checkpoint inhibitors, remain to be confirmed directly in human MDSC. Future studies will apply genomics and proteomics to identify MDSC-specific markers or mechanisms shared in mice and humans. These approaches could elucidate the heterogeneity and functional differences these highly plastic cells adopt in particular microenvironments.)

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