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https://www.readbyqxmd.com/read/28317413/mesenchymal-stromal-cells-enhance-the-suppressive-effects-ofmyeloid-derived-suppressor-cells-of-multiple-myeloma
#1
Yinhui Xu, Xiaoying Zhang, Hongbo Liu, Pan Zhao, Yafang Chen, Yimin Luo, Limin Luo, Zhiqing Zhang, Xiaofang Wang
Both mesenchymal stromal cells (MSCs) and myeloid-derived suppressor cells (MDSCs) have immunosuppressive properties, and their presence may confer a worse prognosis upon cancer patients. However, whether MSCs can enhance the immunosuppressive effects of MDSCs in MM remains unknown. We evaluated the influence of MSCs on MDSCs growth, apoptosis, and functions. Our results show that MSCs promote proliferation and inhibit apoptosis in MDSCs. Additionally, MSCs enhance the ability of MDSCs by inhibiting T-cell proliferation and IFN-γ production...
March 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28314212/gene-delivery-of-tipe2-inhibits-breast-cancer-development-and-metastasis-via-cd8-t-and-nk-cell-mediated-antitumor-responses
#2
Zhenhua Zhang, Li Liu, Shousong Cao, Yizhun Zhu, Qibing Mei
Breast cancer is the second leading cause of cancer-related deaths in the female patients which was mainly caused by metastasis. Development of target gene therapy for breast cancer to suppress tumor progress and metastasis will improve the therapeutic options and be of great benefit to the patients. Tumor necrosis factor-alpha-induced protein 8-like 2 is a novel molecule for maintaining immune homeostasis and is involved in cancer development. In the present study, we overexpressed TIPE2 in breast cancer cells to investigate the role of TIPE2 in the development of breast cancer...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28292944/the-mazy-case-of-notch-and-immunoregulatory-cells
#3
REVIEW
Paola Grazioli, Maria Pia Felli, Isabella Screpanti, Antonio Francesco Campese
The Notch pathway represents a conserved signal transduction machinery that is straightforward and based on a few elements (ligands, receptors, transducers). However, the existence of multiple control levels of the Notch signaling final outcome makes it strictly context dependent and dose dependent. The function of Notch as a regulator of cell development and differentiation, as well as the aberrant consequences of its modulation, either positive or negative, is well established. In this review, we will discuss our current knowledge about Notch-dependent regulation of generation and function of 2 subsets of the immunoregulatory system, namely regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs)...
March 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28288993/a-combined-pd-1-c5a-blockade-synergistically-protects-against-lung-cancer-growth-and-metastasis
#4
Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, Maria J Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J Lasarte, Silvestre Vicent, Axel Vater, Fernando Lecanda, Luis M Montuenga, Ruben Pio
Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that a combined inhibition of C5a/C5aR1 and PD-1 signaling may have an antitumor synergistic effect. RMP1-14 antibody was used to block PD-1 and an L-aptamer to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer we demonstrate that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis, and leads to prolonged survival...
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#5
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28287112/glucocorticoid-receptor-promotes-the-function-of-myeloid-derived-suppressor-cells-by-suppressing-hif1%C3%AE-dependent-glycolysis
#6
Yun Lu, Huanrong Liu, Yujing Bi, Hui Yang, Yan Li, Jian Wang, Zhengguo Zhang, Yu Wang, Chunxiao Li, Anna Jia, Linian Han, Ying Hu, Yong Zhao, Ruoning Wang, Guangwei Liu
Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28276713/aberrant-function-of-myeloid-derived-suppressor-cells-mdscs-in-experimental-colitis-and-in-inflammatory-bowel-disease-ibd-immune-responses
#7
Eleni Kontaki, Dimitrios T Boumpas, Maria Tzardi, Ioannis A Mouzas, Konstantinos A Papadakis, Panayotis Verginis
BACKGROUND AND AIMS: Myeloid-derived suppressor cells (MDSCs) encompass a novel population of suppressor cells and a potential candidate for cell-based therapies in inflammatory diseases. Herein, we investigated their immunomodulatory properties in experimental inflammatory colitis and T cell-mediated immune responses in inflammatory bowel disease (IBD) patients. METHODS: MDSCs (defined as CD14(-)HLA(-)DR(-/low)CD33(+)CD15(+)) numbers were determined in peripheral blood (PB) from IBD patients...
March 3, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28276625/nkg2d-ligand-rae1%C3%AE%C2%B5-induces-generation-and-enhances-the-inhibitor-function-of-myeloid-derived-suppressor-cells-in-mice
#8
Li Qian, Yang Liu, Shaoqing Wang, Weijuan Gong, Xiaoqin Jia, Lu Liu, Feng Ye, Jingjuan Ding, Yuwei Xu, Yi Fu, Fang Tian
Expression of surface NKG2D ligands on tumour cells, which activates nature killer (NK) cells and CD8(+) T cells, is crucial in antitumour immunity. Some types of tumours have evolved mechanisms to suppress NKG2D-mediated immune cell activation, such as tumour-derived soluble NKG2D ligands or sustained NKG2D ligands produced by tumours down-regulate the expression of NKG2D on NK cells and CD8(+) T cells. Here, we report that surface NKG2D ligand RAE1ε on tumour cells induces CD11b(+) Gr-1(+) myeloid-derived suppressor cell (MDSC) via NKG2D in vitro and in vivo...
March 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28256014/transcription-factor-egr1-promotes-differentiation-of-bovine-skeletal-muscle-satellite-cells-by-regulating-myog-gene-expression
#9
Weiwei Zhang, Huili Tong, Ziheng Zhang, Shuli Shao, Dan Liu, Shufeng Li, Yunqin Yan
The transcription factor, early growth response 1 (EGR1), has important roles in various cell types in response to different stimuli. EGR1 is thought to be involved in differentiation of bovine skeletal muscle-derived satellite cells (MDSCs); however, the precise effects of EGR1 on differentiation of MDSCs and its mechanism of action remain unknown. In the present study, a time course of EGR1 expression and the effects of EGR1 on MDSC differentiation were determined. The results demonstrated that the expression of EGR1 mRNA and protein increased significantly in differentiating MDSCs relative to that in proliferating cells...
March 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28249921/mir-20b-induced-increase-in-myeloid-derived-suppressor-cells-in-the-lungs-of-mice-with-chronic-asthma
#10
Hua Ma, Helong Wang, Yulan Luo, Shujun Guo, Chuanwang Song
Bronchial asthma is a common chronic airway inflammatory disease. MicroRNAs (miRNAs) play an important role in the pathogenesis of asthma. We have previously shown that miR-20b can inhibit airway inflammation in asthmatic mice, but the exact mechanism is unknown. In the present study, we show that administration of nasal drops containing miR-20b induced an increase in the percentage of Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs) in lung tissue from asthmatic mice, and the content of TGF-β in lung tissues also increased after treatment...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28243237/critical-role-of-myeloid-derived-suppressor-cells-in-tumor-induced-liver-immune-suppression-through-inhibition-of-nkt-cell-function
#11
Hongru Zhang, Zheng Li, Li Wang, Gaofei Tian, Jun Tian, Zishan Yang, Guangchao Cao, Hong Zhou, Liqing Zhao, Zhenzhou Wu, Zhinan Yin
Metastasis followed by the tumor development is the primary cause of death for cancer patients. However, the underlying molecular mechanisms of how the growth of tumor resulted in the immune suppression, especially at the blood-enriched organ such as liver, were largely unknown. In this report, we studied the liver immune response of tumor-bearing (TB) mice using concanavalin A (Con A)-induced hepatitis model. We demonstrated that TB mice displayed an immune suppression phenotype, with attenuated alanine aminotransferase levels and liver damage upon Con A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28229533/expansion-of-myeloid-derived-suppressor-cells-with-aging-in-the-bone-marrow-of-mice-through-a-nf-%C3%AE%C2%BAb-dependent-mechanism
#12
Rafael R Flores, Cheryl L Clauson, Joonseok Cho, Byeong-Chel Lee, Sara J McGowan, Darren J Baker, Laura J Niedernhofer, Paul D Robbins
With aging, there is progressive loss of tissue homeostasis and functional reserve, leading to an impaired response to stress and an increased risk of morbidity and mortality. A key mediator of the cellular response to damage and stress is the transcription factor NF-κB. We demonstrated previously that NF-κB transcriptional activity is upregulated in tissues from both natural aged mice and in a mouse model of a human progeroid syndrome caused by defective repair of DNA damage (ERCC1-deficient mice). We also demonstrated that genetic reduction in the level of the NF-κB subunit p65(RelA) in the Ercc1(-/∆) progeroid mouse model of accelerated aging delayed the onset of age-related pathology including muscle wasting, osteoporosis, and intervertebral disk degeneration...
February 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28225866/circulating-myeloid-derived-suppressor-cells-predict-disease-activity-and-treatment-response-in-patients-with-immune-thrombocytopenia
#13
J Zhou, Y Zhou, J Wen, X Sun, X Zhang
Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells' differentiation and maturation...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28224211/mechanisms-overseeing-myeloid-derived-suppressor-cell-production-in-neoplastic-disease
#14
REVIEW
Colleen S Netherby, Scott I Abrams
Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28223316/energy-metabolism-drives-myeloid-derived-suppressor-cell-differentiation-and-functions-in-pathology
#15
REVIEW
Antonio Sica, Laura Strauss
Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes...
February 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28221243/effects-of-glycyrrhizin-on-the-differentiation-of-myeloid-cells-of-the-heart-and-lungs-in-lipopolysaccharide-induced-septic-mice
#16
Eun-Hye Seo, Ga-Yun Song, Byung Ok Kwak, Chung-Sik Oh, Seung Hyun Lee, Seong-Hyop Kim
BACKGROUND: This study investigated the effects of glycyrrhizin (GR) on the ratio of myeloid-derived suppressor cells (MDSCs) to cluster of differentiation (CD)11b+Gr1 myeloid cells in the heart and lungs in lipopolysaccharide (LPS)-induced septic mice. METHODS: Mice were divided into three groups: Control, LPS, and LPS+GR. After intraperitoneal injection of phosphate-buffered saline for the Control group, LPS for the LPS group, and a combination of LPS and GR for the LPS+GR group, fluorescence-activated cell sorting was utilized to evaluate cytokines and immune cells in the blood, heart, and lungs...
February 17, 2017: Shock
https://www.readbyqxmd.com/read/28218904/the-protumorigenic-potential-of-fty720-by-promoting-extramedullary-hematopoiesis-and-mdsc-accumulation
#17
Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, J C Morris, E N Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li, G Chen
FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#18
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28215666/expansion-of-polymorphonuclear-myeloid-derived-suppressor-cells-in-patients-with-end-stage-renal-disease-may-lead-to-infectious-complications
#19
Yan-Fang Xing, Rui-Ming Cai, Qu Lin, Qing-Jian Ye, Jian-Hua Ren, Liang-Hong Yin, Xing Li
Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses...
February 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#20
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
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