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https://www.readbyqxmd.com/read/28110209/expansion-of-cd11b-ly-6c-myeloid-derived-suppressor-cells-mdscs-driven-by-galectin-9-attenuates-cvb3-induced-myocarditis
#1
Yingying Zhang, Mengying Zhang, Xueqin Li, Zongsheng Tang, Ling He, Kun Lv
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b(+)Ly-6C(+) MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C(+) MDSCs, but not Ly6G(+) cells, expressed Arg-1 and NOS2, and suppressed CD4(+) T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine...
January 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28109867/interactions-between-interleukin-6-and-myeloid-derived-suppressor-cells-drive-the-chemoresistant-phenotype-of-hepatocellular-cancer
#2
Min Xu, Zhongwei Zhao, Jingjing Song, Xilin Lan, Siming Lu, Minjiang Chen, Zufei Wang, Weiqian Chen, Xiaoxi Fan, Fazong Wu, Li Chen, Jianfei Tu, Jiansong Ji
Emerging evidence implicates an important role for myeloid-derived suppressor cells (MDSCs) in tumor growth, angiogenesis and metastasis. However, limited knowledge is known about the function of MDSCs in response to chemotherapies. In this study, we find that drug-resistant hepatocellular cancer (HCC) cells-derived conditioned medium significantly enhances the expansion and immunosuppressive function of MDSCs compared to their parental sensitive cells, which is demonstrated by increased level of arginase, nitric oxide (NO), and reactive oxygen species (ROS)...
January 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28108766/immunosuppressive-myeloid-derived-suppressor-cells-are-increased-in-splenocytes-from-cancer-patients
#3
Kimberly R Jordan, Puja Kapoor, Eric Spongberg, Richard P Tobin, Dexiang Gao, Virginia F Borges, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice...
January 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28108746/myeloid-derived-suppressor-cells-can-be-efficiently-generated-from-human-hematopoietic-progenitors-and-peripheral-blood-monocytes
#4
Sílvia Casacuberta-Serra, Marta Parés, Arantxa Golbano, Elisabet Coves, Carmen Espejo, Jordi Barquinero
Myeloid-derived suppressor cells (MDSCs) play an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex-vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34(+) hematopoietic progenitors from apheresis products and CD14(+) cells isolated from buffy coats were cultured in the presence of different combinations of cytokines...
January 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#5
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in cancer patients is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T helper (Th1) cells and CD8(+) T cells were directly counter-balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity towards CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DCs), and polarization of macrophages toward the M2 phenotype...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#6
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#7
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28103506/the-effect-of-anti-angiogenic-drugs-on-regulatory-t-cells-in-the-tumor-microenvironment
#8
REVIEW
Chenxi Hu, Xiaodong Jiang
A benefit of anti-angiogenic drugs is improved tumor immune tolerance. Regulatory T cells (Tregs) in the tumor microenvironment mediate tumor immune tolerance and anti-angiogenic drugs not only indirectly affect Tregs via dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) but they can also act directly on Tregs causing immunosuppression. Specifically, these drugs may induce differentiation and chemotaxis and reduce the number and function of Tregs by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) on the cell surface...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28102051/t-cell-immunoglobulin-mucin-3-blockade-drives-an-antitumor-immune-response-in-head-and-neck-cancer
#9
Jian-Feng Liu, Si-Rui Ma, Liang Mao, Lin-Lin Bu, Guang-Tao Yu, Yi-Cun Li, Cong-Fa Huang, Wei-Wei Deng, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
T-cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8(+) T cells and CD11b(+) CD33(+) myeloid-derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression...
December 15, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28101225/monocytic-myeloid-derived-suppressor-cells-as-a-potent-suppressor-of-tumor-immunity-in-non-small-cell-lung-cancer
#10
Katarzyna Pogoda, Maria Pyszniak, Paweł Rybojad, Jacek Tabarkiewicz
Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099502/clinical-and-immune-effects-of-lenalidomide-in-combination-with-gemcitabine-in-patients-with-advanced-pancreatic-cancer
#11
Gustav J Ullenhag, Fariba Mozaffari, Mats Broberg, Håkan Mellstedt, Maria Liljefors
PURPOSE: To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1...
2017: PloS One
https://www.readbyqxmd.com/read/28097660/in-brief-myeloid-derived-suppressor-cells-in-cancer
#12
S Solito, L Pinton, S Mandruzzato
The role of myeloid-derived suppressor cells (MDSCs) in cancer development has become clear over recent years and MDSC targeting is an emerging opportunity for enhancing the effectiveness of current anti-cancer therapies. Since MDSCs are not only able to limit anti-tumour T cell responses, but also promote tumour angiogenesis and invasion, their monitoring has prognostic and predictive value. Herein we review the key features of MDSCs in cancer promotion.
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#13
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28095355/immune-regulatory-network-in-successful-pregnancy-and-reproductive-failures
#14
REVIEW
Mahnaz Ghaebi, Mohammad Nouri, Aliyeh Ghasemzadeh, Laya Farzadi, Farhad Jadidi-Niaragh, Majid Ahmadi, Mehdi Yousefi
Maternal immune system must tolerate semiallogenic fetus to establish and maintain a successful pregnancy. Despite the existence of several strategies of trophoblast to avoid recognition by maternal leukocytes, maternal immune system may react against paternal alloantigenes. Leukocytes are important components in decidua. Not only T helper (Th)1/Th2 balance, but also regulatory T (Treg) cells play an important role in pregnancy. Although the frequency of Tregs is elevated during normal pregnancies, their frequency and function are reduced in reproductive defects such as recurrent miscarriage and preeclampsia...
January 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28092866/transmembrane-tumor-necrosis-factor-%C3%AE-promotes-the-recruitment-of-mdscs-to-tumor-tissue-by-upregulating-cxcr4-expression-via-tnfr2
#15
Hongping Ba, Baihua Li, Xiaoyan Li, Cheng Li, Anlin Feng, Yazhen Zhu, Jing Wang, Zhuoya Li, Bingjiao Yin
Myeloid-derived suppressor cells (MDSCs) accumulated in tumor sites promote immune evasion. We found that TNFR deficiency-induced rejection of transplanted tumor was accompanied with markedly decreased accumulation of MDSCs. However, the mechanism(s) behind this phenomenon is not completely understood. Here, we demonstrated that TNFR deficiency did not affect the amount of MDSCs in bone marrow (BM), but decreased accumulation of Gr-1(+)CD11b(+) MDSCs in the spleen and tumor tissues. The chemotaxis of Tnfr(-/-) MDSCs was prominently decreased in response to both tumor cell culture supernatants and tumor tissue homogenates from Tnfr(-/-) and wild-type mice, indicating an effect of TNFR signaling on chemokine receptor expression in MDSCs...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28092673/irf7-regulates-the-development-of-granulocytic-myeloid-derived-suppressor-cells-through-s100a9-transrepression-in-cancer
#16
Q Yang, X Li, H Chen, Y Cao, Q Xiao, Y He, J Wei, J Zhou
Accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles against achieving appropriate anti-tumor immune responses and successful tumor immunotherapy. Granulocytic MDSCs (G-MDSCs) are common in tumor-bearing hosts. However, the mechanisms regulating the development of MDSCs, especially G-MDSCs, remain poorly understood. In this report, we showed that interferon regulatory factor 7 (IRF7) plays an important role in the development of G-MDSCs, but not monocytic MDSCs. IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#17
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28076241/phenotypic-and-functional-characteristics-of-hla-dr-neutrophils-in-brazilians-with-cutaneous-leishmaniasis
#18
Richard E Davis, Smriti Sharma, Jacilara Conceição, Pedro Carneiro, Fernanda Novais, Phillip Scott, Shyam Sundar, Olivia Bacellar, Edgar M Carvalho, Mary E Wilson
The protozoan Leishmania braziliensis causes cutaneous leishmaniasis (CL) in endemic regions. In murine models, neutrophils (PMNs) are recruited to the site of infection soon after parasite inoculation. However, the roles of neutrophils during chronic infection and in human disease remain undefined. We hypothesized that neutrophils help maintain a systemic inflammatory state in subjects with CL. Lesion biopsies from all patients with CL tested contained neutrophils expressing HLA-DR, a molecule thought to be restricted to professional antigen-presenting cells...
October 17, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28070996/distribution-and-differentiation-of-myeloid-derived-suppressor-cells-after-fluid-resuscitation-in-mice-with-hemorrhagic-shock
#19
Jiu-Kun Jiang, Wen Fang, Liang-Jie Hong, Yuan-Qiang Lu
OBJECTIVE: To investigate the distribution and differentiation of myeloid-derived suppressor cells (MDSCs) in hemorrhagic shock mice, which are resuscitated with normal saline (NS), hypertonic saline (HTS), and hydroxyethyl starch (HES). METHODS: BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups (n=8) in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs (M-MDSCs), and granulocytic/neutrophilic MDSCs (G-MDSCs) in peripheral blood nucleated cells (PBNCs), spleen single-cell suspension, and bone marrow nucleated cells (BMNCs)...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#20
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
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