Editorial

3 pages, 189 KiB

Open AccessEditorial

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 1359

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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11 pages, 2144 KiB

Open AccessArticle

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 13 | Viewed by 2056

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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23 pages, 1079 KiB

Open AccessReview

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 5 | Viewed by 2496

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

Open AccessReview

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 4 | Viewed by 3124

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

Open AccessReview

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 - 04 Aug 2021

Cited by 9 | Viewed by 2747

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

Open AccessReview

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 35 | Viewed by 6907

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

Open AccessReview

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 15 | Viewed by 4025

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

Open AccessReview

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 23 | Viewed by 3134

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

Open AccessReview

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 2133

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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