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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/29456539/generation-of-human-immunosuppressive-myeloid-cell-populations-in-human-interleukin-6-transgenic-nog-mice
#1
Asami Hanazawa, Ryoji Ito, Ikumi Katano, Kenji Kawai, Motohito Goto, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456536/janus-faced-myeloid-derived-suppressor-cell-exosomes-for-the-good-and-the-bad-in-cancer-and-autoimmune-disease
#2
REVIEW
Margot Zöller
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29453429/human-neutrophils-can-mimic-myeloid-derived-suppressor-cells-pmn-mdsc-and-suppress-microbead-or-lectin-induced-t-cell-proliferation-through-artefactual-mechanisms
#3
Dmitri Negorev, Ulf H Beier, Tianyi Zhang, Jon G Quatromoni, Pratik Bhojnagarwala, Steven M Albelda, Sunil Singhal, Evgeniy Eruslanov, Falk W Lohoff, Matthew H Levine, Joshua M Diamond, Jason D Christie, Wayne W Hancock, Tatiana Akimova
We report that human conventional CD15 + neutrophils can be isolated in the peripheral blood mononuclear cell (PBMC) layer during Ficoll gradient separation, and that they can impair T cell proliferation in vitro without concomitant neutrophil activation and killing. This effect was observed in a total of 92 patients with organ transplants, lung cancer or anxiety/depression, and in 18 healthy donors. Although such features are typically associated in the literature with the presence of certain myeloid-derived suppressor cell (PMN-MDSC) populations, we found that commercial centrifuge tubes that contained membranes or gels for PBMC isolation led to up to 70% PBMC contamination by CD15 + neutrophils, with subsequent suppressive effects in certain cellular assays...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452101/socs3-deficiency-in-myeloid-cells-promotes-retinal-degeneration-and-angiogenesis-through-arginase-1-up-regulation-in-experimental-autoimmune-uveoretinitis
#4
Mei Chen, Jiawu Zhao, Imran Ha Ali, Stephen Marry, Josy Augustine, Mohajeet Bhuckory, Aisling Lynch, Adrien Kissenpfennig, Heping Xu
The suppressor of cytokine signalling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysM Cre/+ SOCS3 fl/fl ). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysM Cre/+ SOCS3 fl/fl mice compared to that in WT mice...
February 13, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29437117/the-cardioprotective-role-of-myeloid-derived-suppressor-cells-in-heart-failure
#5
Ling Zhou, Kun Miao, Bingjiao Yin, Huaping Li, Jiahui Fan, Yazhen Zhu, Hongping Ba, Zunyue Zhang, Fang Chen, Jing Wang, Chunxia Zhao, Zhuoya Li, Dao Wen Wang
Background -Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand in cancer, inflammation, and infection and negatively regulate inflammation and the immune response. Heart failure (HF) is a complex clinical syndrome, wherein inflammation induction and incomplete resolution can potentially contribute to HF development and progression. However, the role of MDSCs in HF remains unclear. Methods -The percentage of MDSCs in HF patients and in mice with pressure overload-induced HF using isoproterenol (ISO) infusion or transverse aortic constriction (TAC), was detected by flow cytometry...
February 1, 2018: Circulation
https://www.readbyqxmd.com/read/29436696/cxcr4-receptor-blockage-reduces-the-contribution-of-tumor-and-stromal-cells-to-the-metastatic-growth-in-the-liver
#6
Aitor Benedicto, Irene Romayor, Beatriz Arteta
The liver is a common site for the metastatic spread of primary malignancies including colorectal cancer, and liver metastasis is a main cause of death in cancer patients. This is due to the complexity of the interactions taking place in the liver between tumor and stromal cells. In fact, cancer‑associated fibroblasts (CAFs) have been shown to support tumor growth through the CXCL12/CXCR4 axis. However, along with cancer cells, myeloid‑derived suppressor cells (MDSCs), immature dendritic cells with immunosuppressive potential, also express CXCR4...
February 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29434884/endostatin-reverses-immunosuppression-of-the-tumor-microenvironment-in-lung-carcinoma
#7
Xiaolin Liu, Weiwei Nie, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li, Jing Liang
Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-17, interferon (IFN)-γ and hypoxia inducible factor (HIF)-1α, following endostatin therapy...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29432078/endogenous-tumor-suppressor-microrna-193b-therapeutic-and-prognostic-value-in-acute-myeloid-leukemia
#8
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R Keith Humphries, Michael A Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo...
February 12, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29423083/betulinic-acid-impairs-metastasis-and-reduces-immunosuppressive-cells-in-breast-cancer-models
#9
An-Qi Zeng, Yan Yu, Yu-Qin Yao, Fang-Fang Yang, Mengya Liao, Lin-Jiang Song, Ya-Li Li, Yang Yu, Yu-Jue Li, Yuan-Le Deng, Shu-Ping Yang, Chen-Juan Zeng, Ping Liu, Yong-Mei Xie, Jin-Liang Yang, Yi-Wen Zhang, Ting-Hong Ye, Yu-Quan Wei
Breast cancer is the most common female cancer with considerable metastatic potential, explaining the need for new candidates that inhibit tumor metastasis. In our study, betulinic acid (BA), a kind of pentacyclic triterpenoid compound derived from birch trees, was evaluated for its anti-metastasis activity in vitro and in vivo. BA decreased the viability of three breast cancer cell lines and markedly impaired cell migration and invasion. In addition, BA could inhibit the activation of stat3 and FAK which resulted in a reduction of matrix metalloproteinases (MMPs), and increase of the MMPs inhibitor (TIMP-2) expression...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29418061/platelets-couple-inflammation-to-tumorigenesis-a-bridge-too-far
#10
Matthew J Flick, Joseph S Palumbo
Platelets were first implicated in the pathogenesis of cancer and inflammatory pathologies decades ago, but an understanding of the mechanisms coupling platelet function to cancer progression is still a work in progress. In their paper, Servais et al. push the field forward by illustrating that platelets represent a crucial link between inflammatory disease and tumorigenesis [1]. This interesting paper presents data showing that platelets promote intestinal tumorigenesis in the context of inflammatory colitis by supporting the recruitment and/or expansion of myeloid-derived suppressor cells (MDSCs)...
February 8, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29416921/inhibition-of-rac-family-protein-impairs-colitis-and-colitis-associated-cancer-in-mice
#11
Yandong Guo, Jing Xiong, Jing Wang, Jing Wen, Fachao Zhi
The prevalence of inflammatory bowel disease (IBD) has increased worldwide and IBD has been demonstrated to promote the development of colorectal cancer. The Rac family of proteins are involved in key mitogenic pathways. However, to the best of our knowledge, no prior studies have investigated the expression and role of Rac on colitis and colitis-associated cancer (CAC). In the current study, Rac expression in patients with colitis was analyzed according to the expression value from NCBI GEO database (GDS3268)...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#12
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29410331/cisplatin-inhibits-the-progression-of-bladder-cancer-by-selectively-depleting-g-mdscs-a-novel-chemoimmunomodulating-strategy
#13
Ke Wu, Ming-Yue Tan, Jun-Tao Jiang, Xing-Yu Mu, Jie-Ren Wang, Wen-Jie Zhou, Xiang Wang, Ming-Qing Li, Yin-Yan He, Zhi-Hong Liu
Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues...
February 1, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29409832/the-tumor-suppressor-cholesterol-metabolite-dendrogenin-a-is-a-new-class-of-lxr-modulator-activating-lethal-autophagy-in-cancers
#14
REVIEW
Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a mammalian cholesterol metabolite recently identified that displays tumor suppressor properties. The discovery of DDA has revealed the existence in mammals of a new metabolic branch in the cholesterol pathway centered on 5,6α-epoxycholesterol and bridging cholesterol metabolism with histamine metabolism. Metabolic studies showed a drop in DDA levels in cancer cells and tumors compared to normal cells, suggesting a link between DDA metabolism deregulation and oncogenesis. Importantly, complementation of cancer cells with DDA induced 1) cancer cell re-differentiation, 2) blockade of 6-oxo-cholestan-3β,5α-diol (OCDO) production, an endogenous tumor promoter and 3) lethal autophagy in tumors...
January 31, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29407325/dexamethasone-prolongs-cardiac-allograft-survival-in-a-murine-model-through-myeloid-derived-suppressor-cells
#15
T Nakao, T Nakamura, K Masuda, T Matsuyama, H Ushigome, E Ashihara, N Yoshimura
BACKGROUND: Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood. MATERIAL AND METHODS: In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29404265/pancreatic-cancer-current-status-and-challenges
#16
Amanda R Muñoz, Divya Chakravarthy, Jingjing Gong, Glenn A Halff, Rita Ghosh, Addanki P Kumar
Purpose of the review: The 5-year survival rate of patients with pancreatic cancer (PanCA) has remained stagnant. Unfortunately, the incidence is almost equal to mortality rates. These facts underscore the importance of concerted efforts to understand the pathology of this disease. Deregulation of multiple signaling pathways involved in a wide variety of cellular processes including proliferation, apoptosis, invasion, and metastasis contribute not only to cancer development but also to therapeutic resistance...
December 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29399415/melanoma-induced-immunosuppression-is-mediated-by-hematopoietic-dysregulation
#17
Neha Kamran, Youping Li, Maria Sierra, Mahmoud S Alghamri, Padma Kadiyala, Henry D Appelman, Marta Edwards, Pedro R Lowenstein, Maria G Castro
Tumors are associated with expansion of immunosuppressive cells such as tumor associated macrophages (TAMs), regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). These cells promote tumor growth, angiogenesis, metastasis and immune escape. Cancer patients frequently present symptoms such as anemia, leukocytosis and/or cytopenia; associated with poor prognosis. To uncover tumor-mediated hematopoietic abnormalities and identify novel targets that can be harnessed to improve tumor-specific immune responses, we investigated the hematopoietic stem and progenitor cell compartment in melanoma bearing mice...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399404/frequent-adaptive-immune-responses-against-arginase-1
#18
Evelina Martinenaite, Rasmus Erik Johansson Mortensen, Morten Hansen, Morten Orebo Holmström, Shamaila Munir Ahmad, Nicolai Grønne Dahlager Jørgensen, Özcan Met, Marco Donia, Inge Marie Svane, Mads Hald Andersen
The enzyme arginase-1 reduces the availability of arginine to tumor-infiltrating immune cells, thus reducing T-cell functionality in the tumor milieu. Arginase-1 is expressed by some cancer cells and by immune inhibitory cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and its expression is associated with poor prognosis. In the present study, we divided the arginase-1 protein sequence into overlapping 20-amino-acid-long peptides, generating a library of 31 peptides covering the whole arginase-1 sequence...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399399/bromodomain-inhibition-exerts-its-therapeutic-potential-in-malignant-pleural-mesothelioma-by-promoting-immunogenic-cell-death-and-changing-the-tumor-immune-environment
#19
Chiara Riganti, Marcello Francesco Lingua, Iris Chiara Salaroglio, Chiara Falcomatà, Luisella Righi, Deborah Morena, Francesca Picca, Daniele Oddo, Joanna Kopecka, Monica Pradotto, Roberta Libener, Sara Orecchia, Paolo Bironzo, Valentina Comunanza, Federico Bussolino, Silvia Novello, Giorgio Vittorio Scagliotti, Federica Di Nicolantonio, Riccardo Taulli
Systemic treatment of malignant pleural mesothelioma (MPM) is moderately active for the intrinsic pharmacological resistance of MPM cell and its ability to induce an immune suppressive environment. Here we showed that the expression of bromodomain (BRD) proteins BRD2, BRD4 and BRD9 was significantly higher in human primary MPM cells compared to normal mesothelial cells (HMC). Nanomolar concentrations of bromodomain inhibitors (BBIs) JQ1 or OTX015 impaired patient-derived MPM cell proliferation and induced cell-cycle arrest without affecting apoptosis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29388481/chemotherapy-alters-the-increased-numbers-of-myeloid-derived-suppressor-and-regulatory-t-cells-in-children-with-acute-lymphoblastic-leukemia
#20
Mohamed Labib Salem, Mohamed R El-Shanshory, Said H Abdou, Mohamed S Attia, Shymaa M Sobhy, Mona F Zidan, Abdel-Aziz A Zidan
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) which we and others have reported to mediate suppression of anti-tumor immune responses. AIM: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients...
February 1, 2018: Immunopharmacology and Immunotoxicology
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