scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 677
Author(s):  
Dorota Suszczyk ◽  
Wiktoria Skiba ◽  
Joanna Jakubowicz-Gil ◽  
Jan Kotarski ◽  
Iwona Wertel
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunological Diseases ◽  
Underlying Mechanisms ◽  
And Function ◽  
The Impact

Endometriosis (EMS) is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus. Approximately 10% of women around the world suffer from this disease. Recent studies suggest that endometriosis has potential to transform into endometriosis-associated ovarian cancer (EAOC). Endometriosis is connected with chronic inflammation and changes in the phenotype, activity, and function of immune cells. The underlying mechanisms include quantitative and functional disturbances of neutrophils, monocytes/macrophages (MO/MA), natural killer cells (NK), and T cells. A few reports have shown that immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) may promote the progression of endometriosis. MDSCs are a heterogeneous population of immature myeloid cells (dendritic cells, granulocytes, and MO/MA precursors), which play an important role in the development of immunological diseases such as chronic inflammation and cancer. The presence of MDSCs in pathological conditions correlates with immunosuppression, angiogenesis, or release of growth factors and cytokines, which promote progression of these diseases. In this paper, we review the impact of MDSCs on different populations of immune cells, focusing on their immunosuppressive role in the immune system, which may be related with the pathogenesis and/or progression of endometriosis and its transformation into ovarian cancer.

scholarly journals Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

2019 ◽  
Vol 29 (9) ◽  
pp. 1381-1388 ◽  
Author(s):  
An Coosemans ◽  
Thaïs Baert ◽  
Jolien Ceusters ◽  
Pieter Busschaert ◽  
Chiara Landolfo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Killer Cells

BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

scholarly journals Regulatory T Cells in Human Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Dong-Jun Peng ◽  
Rebecca Liu ◽  
Weiping Zou
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Suppression ◽  
Immune Cells ◽  
Clinical Settings ◽  
Human Ovarian Cancer ◽  
Cancer Microenvironment ◽  
Cellular Mechanisms ◽  
And Function ◽  
Antigen Presenting

Multiple layers of suppressive components including regulatory T (TReg) cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TRegcells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TRegcells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TRegcells in preclinical and clinical settings.

scholarly journals Modulation of Immunity by Antiangiogenic Molecules in Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Magali Terme ◽  
Orianne Colussi ◽  
Elie Marcheteau ◽  
Corinne Tanchot ◽  
Eric Tartour ◽  
...  
Keyword(s):  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunomodulatory Effects ◽  
New Class ◽  
Immune Parameters ◽  
Therapeutic Drugs ◽  
The Impact ◽  
Immunosuppressive Cytokines ◽  
Potential Biomarkers

In the last decades a new class of therapeutic drugs have been developed that block tumor angiogenesis. These antiangiogenic molecules, which target VEGF or VEGFR, PDGFR, and c-kit, can act not only on endothelial cells but also on immune cells. Some antiangiogenic molecules inhibit the development of immunosuppressive mechanisms developed by the tumors to escape the immune system (such as regulatory T cells, myeloid-derived suppressor cells, and immunosuppressive cytokines). These immunomodulatory effects must be characterized in detail to enable a better prescription of these treatments. In this paper we will focus on the impact of anti-angiogenic drugs on immunosuppression and their potential combination with immunotherapeutic strategies. Interestingly, immune parameters or their modulation during treatment could serve as potential biomarkers of response or resistance to anti-angiogenic therapies.

scholarly journals Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin

2019 ◽  
Vol 25 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Young Suk Lee ◽  
Eduardo Davila ◽  
Tianshu Zhang ◽  
Hugh P Milmoe ◽  
Stefanie N Vogel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Suppressor Cells ◽  
Arginase Activity ◽  
T Cell Proliferation ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
And Function

Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro, ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30–40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation.

scholarly journals Immunosuppressive B cells expressing PD-1/PD-L1 in solid tumors: A mini review

QJM ◽  
2019 ◽  
Author(s):  
Xiaowen Sun ◽  
Tingyou Zhang ◽  
Mengqian Li ◽  
Limei Yin ◽  
Jianxin Xue
Keyword(s):  
T Cells ◽  
Cell Death ◽  
B Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Diagnostic Tools ◽  
Myeloid Derived Suppressor Cells ◽  
Programmed Cell Death 1 ◽  
B Cell Subsets

Abstract Expression of Programmed Cell Death-1 (PD-1/CD279) on T cells and the ligand of PD-1, PD-L1 (CD274/B7-H1) on tumor cells or other immune cells, such as myeloid-derived suppressor cells, are important mechanisms to induce malignant immunosuppression. PD-1/PD-L1 expression on B cell subsets, as well as their signaling and inhibitory functions in solid tumors will be discussed in this review with the focus on how B cells expressing PD-1/PD-L1 play immunosuppressive roles in tumor progression, aiming to figure out the potential for development of diagnostic tools and new therapies involving this unique group of cells.

scholarly journals The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Maximilian Haist ◽  
Henner Stege ◽  
Stephan Grabbe ◽  
Matthias Bros
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
T Cell Activation ◽  
Metastatic Cancer ◽  
Suppressor Cells ◽  
Cell Populations ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Cell ◽  
The Impact

Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.

scholarly journals Repression of MUC1 Promotes Expansion and Suppressive Function of Myeloid-Derived Suppressor Cells in Pancreatic and Breast Cancer Murine Models

2021 ◽  
Vol 22 (11) ◽  
pp. 5587
Author(s):  
Mahnaz Sahraei ◽  
Mukulika Bose ◽  
J. Alexa Sanders ◽  
Chandrav De ◽  
Lopamudra DasRoy ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cell Function ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Transmembrane Glycoprotein ◽  
Suppressive Phenotype ◽  
The Impact

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing syngeneic pancreatic (KCKO) or breast (C57MG) tumors. We observed enhanced tumor growth of pancreatic and breast tumors in the MUC1KO mice compared to the WT mice. Enhanced tumor growth in the MUC1KO mice was associated with increased numbers of suppressive MDSCs and T regulatory (Tregs) cells in the tumor microenvironment. Compared to the WT host, MUC1KO host showed higher levels of iNOS, ARG1, and TGF-β, thus promoting proliferation of MDSCs with an immature and immune suppressive phenotype. When co-cultured with effector T cells, MDSCs from MUC1KO mice led to higher repression of IL-2 and IFN-γ production by T cells as compared to MDSCs from WT mice. Lastly, MDSCs from MUC1KO mice showed higher levels of c-Myc and activated pSTAT3 as compared to MDSCs from WT mice, suggesting increased survival, proliferation, and prevention of maturation of MDSCs in the MUC1KO host. We report diminished T cell function in the KO versus WT mice. In summary, the data suggest that MUC1 may regulate signaling pathways that are critical to maintain the immunosuppressive properties of MDSCs.

Sympathetic nervous tone limits the development of myeloid-derived suppressor cells

2020 ◽  
Vol 5 (51) ◽  
pp. eaay9368 ◽  
Author(s):  
James T. Nevin ◽  
Marmar Moussa ◽  
William L. Corwin ◽  
Ion I. Mandoiu ◽  
Pramod K. Srivastava
Keyword(s):  
Tumor Immunity ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Sympathetic Nerves ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
Adaptive Immune Cells ◽  
Promote Tumor Growth ◽  
Sympathetic Nervous ◽  
And Function

Sympathetic nerves that innervate lymphoid organs regulate immune development and function by releasing norepinephrine that is sensed by immune cells via their expression of adrenergic receptors. Here, we demonstrate that ablation of sympathetic nervous system (SNS) signaling suppresses tumor immunity, and we dissect the mechanism of such immune suppression. We report that disruption of the SNS in mice removes a critical α-adrenergic signal required for maturation of myeloid cells in normal and tumor-bearing mice. In tumor-bearing mice, disruption of the α-adrenergic signal leads to the accumulation of immature myeloid-derived suppressor cells (MDSCs) that suppress tumor immunity and promote tumor growth. Furthermore, we show that these SNS-responsive MDSCs drive expansion of regulatory T cells via secretion of the alarmin heterodimer S100A8/A9, thereby compounding their immunosuppressive activity. Our results describe a regulatory framework in which sympathetic tone controls the development of innate and adaptive immune cells and influences their activity in health and disease.

scholarly journals Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

2020 ◽  
Vol 21 (16) ◽  
pp. 5647 ◽  
Author(s):  
Jan Korbecki ◽  
Klaudyna Kojder ◽  
Katarzyna Barczak ◽  
Donata Simińska ◽  
Izabela Gutowska ◽  
...  
Keyword(s):  
T Cells ◽  
Chemokine Receptors ◽  
Oxygen Deficiency ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Hypoxia Inducible Factors ◽  
Cc Chemokine ◽  
Neoplastic Processes ◽  
Cc Chemokines ◽  
The Impact

Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

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