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https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#1
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#2
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#3
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722681/the-role-of-toll-like-receptor-4-in-tumor-microenvironment
#4
REVIEW
Jing Li, Fan Yang, Feng Wei, Xiubao Ren
Tumors are closely related to chronic inflammation, during which there are various changes in inflammatory sites, such as immune cells infiltration, pro-inflammation cytokines production, and interaction between immune cells and tissue cells. Besides, substances, released from both tissue cells attacked by exogenous etiologies, also act on local cells. These changes induce a dynamic and complex microenvironment favorable for tumor growth, invasion, and metastasis. The toll-like receptor 4 (TLR4) is the first identified member of the toll-like receptor family that can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMPs)...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#5
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711922/hmgb1-promotes-myeloid-derived-suppressor-cells-and-renal-cell-carcinoma-immune-escape
#6
Jinfeng Li, Jiajia Sun, Ruiming Rong, Long Li, Wenjun Shang, Dongkui Song, Guiwen Feng, Feifei Luo
Despite high immunogenicity and marked presence of immune cells in the RCC(renal cell carcinoma), immunotherapy fails to develop effective anti-tumor immune responses. This is due to the negative regulatory factors in the tumor microenvironment. As the main contributor of immunosuppression, myeloid-derived suppressor cells (MDSCs) inhibited anti-tumor immunity and promoted tumor progression. Meanwhile, it is confirmed that high mobility group box-1 protein (HMGB1) shows a high expression in many solid tumors and HMGB1 with high expression is involved in tumor immune escape...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698201/entinostat-neutralizes-myeloid-derived-suppressor-cells-and-enhances-the-antitumor-effect-of-pd-1-inhibition-in-murine-models-of-lung-and-renal-cell-carcinoma
#7
Ashley Orillion, Ayumi Hashimoto, Nur P Damayanti, Li Shen, Remi Adelaiye-Ogala, Sreevani Arisa, Sreenivasulu Chintala, Peter Ordentlich, Chinghai Kao, Bennett Elzey, Dmitry Gabrilovich, Roberto Pili
Purpose: Recent advances in immunotherapy highlight the antitumor effects of immune- checkpoint inhibition despite a relatively limited subset of patients receiving clinical benefit. The selective class I histone deacetylase inhibitor (HDACi) entinostat has been reported to have immunomodulatory activity including targeting of immune suppressor cells in the tumor microenvironment. Thus, we decided to assess whether entinostat could enhance anti-PD-1 treatment and investigate those alterations in the immunosuppressive tumor microenvironment that contribute to the combined anti-tumor activity...
July 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28693175/functional-analysis-of-cd14-hla-dr-low-myeloid-derived-suppressor-cells-in-patients-with-lung-squamous-cell-carcinoma
#8
Yun Chen, Guichang Pan, Dongbo Tian, Yifei Zhang, Taoping Li
Immunomodulatory therapy is a potential effective treatment for advanced cancer that may provide an alternative to chemotherapy, which patients can experience adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to cause T-cell tolerance in rodents and humans; however, little is known about the role of MDSCs in squamous cell carcinoma. In the present study, the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls was examined for the presence and function of human MDSCs, denoted as monocyte differentiation antigen CD14-positive HLA class II histocompatibility antigen DR-negative/low (CD14(+) HLA-DR(-/low)) cells by flow cytometry...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687234/myeloid-derived-suppressor-cells-modulate-b-cell-responses
#9
Felipe J N Lelis, Jennifer Jaufmann, Anurag Singh, Katja Fromm, Annkathrin Chiara Teschner, Simone Pöschel, Iris Schäfer, Sandra Beer-Hammer, Nikolaus Rieber, Dominik Hartl
Myeloid-derived suppressor cells (MDSCs) are key regulators of adaptive immunity by suppressing T-cell functions. However, their potential action on or interaction with B cells remained poorly understood. Here we demonstrate that human polymorphonuclear MDSCs differentially modulate B-cell function by suppressing B-cell proliferation and antibody production. We further demonstrate that this MDSC-mediated effect is cell contact dependent and involves established mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as well as B-cell death...
July 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28682942/protection-against-lipopolysaccharide-induced-immunosuppression-by-igg-and-igm
#10
Christiana Kyvelidou, Dimitris Sotiriou, Ioanna Zerva, Irene Athanassakis
Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the potential role of IgG and IgM in reversing LPS endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2 μg/g LPS, which was tolerable by half of the manipulated animals. Such protocol allowed longer survival, necessary in the prospect of therapeutic treatment application...
July 4, 2017: Shock
https://www.readbyqxmd.com/read/28680754/cd39-cd73-upregulation-on-myeloid-derived-suppressor-cells-via-tgf-%C3%AE-mtor-hif-1-signaling-in-patients-with-non-small-cell-lung-cancer
#11
Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Yu Ping, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Li Yang, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo Huang, Bin Zhang, Yi Zhang
CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b(+)CD33(+) myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28676100/superior-gvhd-free-relapse-free-survival-for-g-bm-to-g-pbsc-grafts-is-associated-with-higher-mdscs-content-in-allografting-for-patients-with-acute-leukemia
#12
Qian Fan, Hui Liu, Xinquan Liang, Ting Yang, Zhiping Fan, Fen Huang, Yiwen Ling, Xin Liao, Li Xuan, Na Xu, Xiaojun Xu, Jieyu Ye, Qifa Liu
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1)...
July 4, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28668887/frequency-of-myeloid-derived-suppressor-cells-in-the-peripheral-blood-reflects-the-status-of-tumor-recurrence
#13
Tomoko Tanaka, Mitsugu Fujita, Hiroshi Hasegawa, Akira Arimoto, Masayasu Nishi, Eiji Fukuoka, Yutaka Sugita, Takeru Matsuda, Yasuo Sumi, Satoshi Suzuki, Yoshihiro Kakeji, Kimihiro Yamashita
BACKGROUND: Malignant tumors inhibit antitumor immune responses, which are driven by T-regulatory cells or myeloid-derived suppressor cells (MDSCs). Since MDSCs are involved in invasion, migration, and metastasis of tumor cells, we hypothesized that MDSCs are also involved in tumor recurrence after surgical resection. MATERIALS AND METHODS: C57BL/6 mice were subcutaneously inoculated with B16F10 melanoma cells in the right flank. In some experiments, established tumors were surgically resected...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666020/modulating-glioma-mediated-myeloid-derived-suppressor-cell-development-with-sulforaphane
#14
Ravi Kumar, Tristan de Mooij, Timothy E Peterson, Tatiana Kaptzan, Aaron J Johnson, David J Daniels, Ian F Parney
Glioblastoma is the most common primary tumor of the brain and has few long-term survivors. The local and systemic immunosuppressive environment created by glioblastoma allows it to evade immunosurveillance. Myeloid-derived suppressor cells (MDSCs) are a critical component of this immunosuppression. Understanding mechanisms of MDSC formation and function are key to developing effective immunotherapies. In this study, we developed a novel model to reliably generate human MDSCs from healthy-donor CD14+ monocytes by culture in human glioma-conditioned media...
2017: PloS One
https://www.readbyqxmd.com/read/28661031/myeloid-derived-suppressor-cells-important-contributors-to-tumor-progression-and-metastasis
#15
REVIEW
Elham Safarzadeh, Mona Orangi, Hamed Mohammadi, Farhad Babai, Behzad Baradaran
Myeloid-derived suppressor cells (MDSCs) are traditionally considered among the major components of the immunosuppressive tumor microenvironment. However, there is currently increasing evidence indicating that MDSCs in addition to suppression of immune surveillance is also involved in an array of non-immunological functions like augmenting metastatic potential of tumor cells. Indeed, MDSCs can promote metastasis in animal models and cancer patients through promoting premetastatic niche formation, tumor angiogenesis and invasion...
June 29, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28657582/biocompatibility-of-hbv-liposome-encapsulated-hemoglobin-molecules-liposome-effects-on-immune-function
#16
REVIEW
Hiroshi Azuma, Mitsuhiro Fujihara, Hiromi Sakai
Hemoglobin vesicles (HbVs) are oxygen carriers consisting of Hb molecules and liposome in which human hemoglobin (Hb) molecules are encapsulated. Investigations of HbV biocompatibility have shown that HbVs have no significant effect on either the quality or quantity of blood components such as RBC, WBC, platelets, complements, or coagulation factors, reflecting its excellent biocompatibility. However, their effects on the immune system remain to be evaluated. HbVs might affect the function of macrophages because they accumulate in the reticuloendothelial system...
June 28, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/28657225/programmed-death-1-pathway-blockade-produces-a-synergistic-antitumor-effect-combined-application-in-ovarian-cancer
#17
REVIEW
Xinxin Zhu, Jinghe Lang
Programmed death-1 (PD-1) and its ligand are part of the immune checkpoint pathway that down-regulates effector T cells in immune response, thereby causing immune suppression. The PD-1/programmed death-ligand 1 (PD-L1) pathway can be blocked by antibodies to reverse tumor-mediated immunosuppression. However, advanced cancers such as stage III-IV ovarian cancer (OC) and certain types such as ID8 OC (a clone of C57BL/6 mouse OC) may hijack the PD-1/PD-L1 pathway to escape immune attack. When combined with chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other agents, these PD-1/PD-L1 pathway blockages can produce a synergistic antitumor response in OC...
June 5, 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28656005/stroma-derived-fibrinogen-like-protein-2-activates-cancer-associated-fibroblasts-to-promote-tumor-growth-in-lung-cancer
#18
Ying Zhu, Longhui Zhang, Haoran Zha, Fei Yang, Chunyan Hu, Lin Chen, Bo Guo, Bo Zhu
Fibrinogen-like protein 2 (Fgl2), a member of the fibrinogen super family, is a pleiotropic cytokine that impacts diverse cellular functions. Previous studies have shown that tumor cell-derived Fgl2 promotes tumorigenesis and metastasis in immune-deficient mice, and it also functions as an immune-suppressive modulator in glioblastoma multiform (GMB). This study aimed to evaluate whether and how tumor stroma-derived Fgl2 affects tumorigenesis and tumor progression. We established the syngeneic transplantable Lewis lung carcinoma (LLC) model in Fgl2-knock-out (Fgl2-KO) mice and we found that deficiency of host Fgl2 is associated with reduced growth of syngeneic LLC tumors...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28654863/stat6-promotes-intestinal-tumorigenesis-in-a-mouse-model-of-adenomatous-polyposis-by-expansion-of-mdscs-and-inhibition-of-cytotoxic-cd8-response
#19
Asha Jayakumar, Alfred L M Bothwell
Intestinal tumorigenesis in the ApcMin/+ model is initiated by aberrant activation of Wnt pathway. Increased IL-4 expression in human colorectal cancer tissue and growth of colon cancer cell lines implied that IL-4-induced Stat6-mediated tumorigenic signaling likely contributes to intestinal tumor progression in ApcMin/+ mice. Stat6 also appears to promote expansion of myeloid-derived suppressor cells (MDSCs) cells. MDSCs promote polyp formation in the ApcMin/+ model. Hence, Stat6 could have a broad role in coordinating both polyp cell proliferation and MDSC expansion...
June 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28651910/taming-the-immune-system-through-transfusion-in-oncology-patients
#20
REVIEW
Seyed Mohammad Amin Kormi, Jerard Seghatchian
Blood transfusion is a clinical replacement therapy with many successes with some benefit and, also, some harm. Cancer is a multifaceted disease potentially associated with the immune system's weakness where the cancerous tumor cells escape from the immune system. Allogeneic blood transfusion, through five major mechanisms including the lymphocyte-T set, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), natural killer cells (NKCs), and dendritic cells (DCs) can help the recipient's defense mechanisms...
May 26, 2017: Transfusion and Apheresis Science
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