scholarly journals Myeloid-derived suppressor cells as a target for anticancer therapy

2018 ◽  
Vol 72 ◽  
pp. 1179-1198
Author(s):  
Natalia Anger ◽  
Joanna Rossowska
Keyword(s):  
Myeloid Cells ◽  
Suppressor Cells ◽  
Immune Checkpoints ◽  
Myeloid Derived Suppressor Cells ◽  
Suppressor Activity ◽  
Premetastatic Niche ◽  
Current State ◽  
Tumor Diagnostics ◽  
Promote Tumor Growth ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells are heterogenic immature myeloid cells, which possess suppressor activity and play an important role in both, tumor progression and metastasis. The accumulation of MDSCs is induced primarily by factors that are secreted by the tumor microenvironment, which disturb myelopoiesis that occurs in the bone marrow and enables the migration of immature myeloid cells into the tumor. MDSCs promote tumor growth by inhibiting the activity of immunocompetent cells, as well as by activating non-immunological processes, such as tumor angiogenesis, the degradation of extracellular matrix and the formation of premetastatic niche. Due to their significant impact on the development of cancer, MDSCs became clinically relevant in tumor diagnostics. In recent years, various therapeutic strategies were developed in order to inhibit the proliferation, accumulation or suppressor activity of MDSCs, as well as to render the differentiation or total depletion of these cells. The proposed therapies often combine factors that reduce MDSCs suppression with conventional chemotherapy or with immune checkpoints inhibitors. In this review, we describe the current state of knowledge about factors that enable the accumulation of MDSCs, methods of phenotypic identification of these cells, as well as the mechanisms of suppression used by them. Moreover, we provide insight into the therapeutic approaches, which aim to restore the reactivity of the immune system by reducing the suppressor effects of MDSCs.

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

2021 ◽  
Vol 11 (1) ◽  
pp. 187
Author(s):  
Nikoleta Bizymi ◽  
Helen A. Papadaki
Keyword(s):  
T Cell ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
T Cell Responses ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunomodulating properties, mainly acting by suppressing T-cell responses [...]

scholarly journals A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2254-2265 ◽  
Author(s):  
Samantha Solito ◽  
Erika Falisi ◽  
Claudia Marcela Diaz-Montero ◽  
Andrea Doni ◽  
Laura Pinton ◽  
...  
Keyword(s):  
Immune Suppression ◽  
Myeloid Cells ◽  
Cell Subset ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Gm Csf ◽  
Immature Myeloid Cells ◽  
Rapid Generation ◽  
Worse Prognosis

Abstract We recently demonstrated that human BM cells can be treated in vitro with defined growth factors to induce the rapid generation of myeloid-derived suppressor cells (MDSCs), hereafter defined as BM-MDSCs. Indeed, combination of G-CSF + GM-CSF led to the development of a heterogeneous mixture of immature myeloid cells ranging from myeloblasts to band cells that were able to suppress alloantigen- and mitogen-stimulated T lymphocytes. Here, we further investigate the mechanism of suppression and define the cell subset that is fully responsible for BM-MDSC–mediated immune suppression. This population, which displays the structure and markers of promyelocytes, is however distinct from physiologic promyelocytes that, instead, are devoid of immuosuppressive function. In addition, we demonstrate that promyelocyte-like cells proliferate in the presence of activated lymphocytes and that, when these cells exert suppressive activity, they do not differentiate but rather maintain their immature phenotype. Finally, we show that promyelocyte-like BM-MDSCs are equivalent to MDSCs present in the blood of patients with breast cancer and patients with colorectal cancer and that increased circulating levels of these immunosuppressive myeloid cells correlate with worse prognosis and radiographic progression.

scholarly journals Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyan Li ◽  
Jiahui Zhong ◽  
Xue Deng ◽  
Xuan Guo ◽  
Yantong Lu ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Therapy Resistance ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Antitumor Efficacy ◽  
Myeloid Derived Suppressor Cells ◽  
Immature Myeloid Cells ◽  
Different Levels

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are activated under pathological conditions, such as cancer, or mature myeloid cells that are converted immune-suppressive cells via tumor-derived exosomes, and potently support the tumor processes at different levels. Currently, multiple studies have demonstrated that MDSCs induce immune checkpoint blockade (ICB) therapy resistance through their contribution to the immunosuppressive network in the tumor microenvironment. In addition, non-immunosuppressive mechanisms of MDSCs such as promotion of angiogenesis and induction of cancer stem cells also exert a powerful role in tumor progression. Thus, MDSCs are potential therapeutic targets to enhance the antitumor efficacy of ICB therapy in cases of multiple cancers. This review focuses on the tumor-promoting mechanism of MDSCs and provides an overview of current strategies that target MDSCs with the objective of enhancing the antitumor efficacy of ICB therapy.

scholarly journals Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clémence Marais ◽  
Caroline Claude ◽  
Nada Semaan ◽  
Ramy Charbel ◽  
Simon Barreault ◽  
...  
Keyword(s):  
Critically Ill ◽  
Host Response ◽  
Secondary Infection ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Human Leukocyte ◽  
Myeloid Derived Suppressor Cells ◽  
Phenotypic Characteristics ◽  
Leukocyte Antigen ◽  
Hla Dr

Abstract Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

scholarly journals Myeloid-derived Suppressor Cells in Cancer: A Review on the Pathogenesis and Therapeutic Potentials

2018 ◽  
Vol 7 (1) ◽  
pp. 16-33
Author(s):  
Seidu A. Richard
Keyword(s):  
Treatment Options ◽  
High Mobility ◽  
Suppressor Cells ◽  
Cancer Development ◽  
Myeloid Derived Suppressor Cells ◽  
Innate Immune Responses ◽  
Cancer Pathogenesis ◽  
Glycation End Products ◽  
Immature Myeloid Cells ◽  
Immature Cells

Myeloid-Derived Suppressor Cells (MDSCs) are multifarious group of immature cells that arise from the myeloid and amass in individuals with cancer, sepsis, burns, or chronic inflammation. It has been evidenced that these group of cells are efficient in modifying adaptive and innate immune responses, coherent with their assumed key biological roles. It is evidenced that MDSCs inter-communicate with Tumor-Associated Macrophages (TAM), Tumor-Associated Neutrophils (TAN), Dendritic Cells (DCs), Receptor for Advanced Glycation End-products (RAGE), Toll-Like Receptors (TLRs), Matrix Metalloproteinase (MMPs) as well as High Mobility Group Box 1 (HMGB1) during carcinogenesis. This interaction although elaborated in various studies and reviews still does not explain in details as to how their interplay results in cancer pathogenesis. We noted that MDSC contributed to cancer immune suppressionviaTLR-4 receptor and lipopolysaccharideas (LPS). Furthermore, MDSC contributed to cancer developmentviaMMPs (MMP-9 and MMP1-12) as well as RAGE. In the cancer microenvironment, HMGB1-driven MDSC amassment expedites cancer development and metastasisviaPMN-MDSCs, macrophages, DCs and Immature Myeloid Cells (IMC). Also, HMGB1 intermediation with MDSCsviaRAGE and/or TLR-4 leading to cancer development. Nevertheless, MDSCs have already proven potent in some cancers and are currently been used as treatment options although further studies are needed in some other cancers. Our review, therefore, explores the pivotal pathogenic and therapeutic roles of MDSCs in cancer.

Abstract 87: The Accumulation of Myeloid-derived Suppressor Cells Is a Compensatory Response to the Development of Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Xiao Z Shen ◽  
Peng Shi ◽  
Jorge Giani ◽  
Ellen Bernstein ◽  
Kenneth E Bernstein
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Compensatory Response ◽  
Immunosuppressive Cell ◽  
Induced Hypertension

The immune system plays a critical role in the development of hypertension. The immune response consists of pro-inflammatory cells, but also immunosuppressive cells that reduce T cell function. An important category of natural immunosuppressive cell is myeloid-derived suppressor cells (MDSC). We now show that blood and spleen CD11b+ Gr1+ myeloid cells are elevated 2-fold in both angiotensin II and L-NAME induced hypertension. These increased myeloid cells are MDSC in that they elevate IL-4R expression and suppress T cell proliferation. When hypertensive mice were depleted of MDSC, using either anti-Gr1 antibody or gemcitabine, there was a 15 mmHg rise in blood pressure and aggravation of T cells activation with increased production of IFN-γ, TNFα and IL-17 in both spleen and kidney. In contrast, adoptive transfer of MDSC reduced blood pressure in angiotensin-II induced hypertension by 25 mmHg (see Figure). These data suggest a new concept, that the accumulation of MDSC is a compensatory response to the inflammation induced by hypertension. They also indicate that MDSC play an important role in regulating blood pressure.

scholarly journals Myeloid-derived suppressor cells in hematological malignancies: friends or foes

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Meng Lv ◽  
Ke Wang ◽  
Xiao-jun Huang
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Tumor Immunology ◽  
Hematological Malignancies ◽  
Inflammatory Diseases ◽  
Suppressor Cells ◽  
Multiple Roles ◽  
Myeloid Derived Suppressor Cells ◽  
Hematopoietic Stem ◽  
Immature Myeloid Cells

Abstract Myeloid-derived suppressor cells (MDSCs) are newly identified immature myeloid cells that are characterized by the ability to suppress immune responses and expand during cancer, infection, and inflammatory diseases. Although MDSCs have attracted a lot of attention in the field of tumor immunology in recent years, little is known about their multiple roles in hematological malignancies as opposed to their roles in solid tumors. This review will help researchers better understand the various characteristics and functions of MDSCs, as well as the potential therapeutic applications of MDSCs in hematological malignancies, including lymphoma, multiple myeloma, leukemia, and hematopoietic stem cell transplantation.

scholarly journals The mechanism of the premetastatic niche facilitating colorectal cancer liver metastasis generated from myeloid-derived suppressor cells induced by the S1PR1–STAT3 signaling pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Qi Lin ◽  
Li Ren ◽  
Mi Jian ◽  
Pingping Xu ◽  
Jun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
T Cell ◽  
Liver Metastasis ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Poor Prognosis ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Premetastatic Niche

Abstract The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1–STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14+HLA-DR−/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1–STAT3–IL-6–MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1–STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

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