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Myeloid-derived suppressor cells

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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
#1
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
#2
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/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#3
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#4
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#5
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28070996/distribution-and-differentiation-of-myeloid-derived-suppressor-cells-after-fluid-resuscitation-in-mice-with-hemorrhagic-shock
#6
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
#7
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
https://www.readbyqxmd.com/read/28062672/repurposing-antiestrogens-for-tumor-immunotherapy
#8
Thomas Welte, Xiang H-F Zhang, Jeffrey M Rosen
Svoronos and colleagues observed estrogen receptor alpha-positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs...
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28060224/granulocytic-myeloid-derived-suppressor-cells-increased-in-early-phases-of-primary-hiv-infection-depending-on-trail-plasma-level
#9
N Tumino, M T Bilotta, C Pinnetti, A Ammassari, A Antinori, F Turchi, C Agrati, R Casetti, V Bordoni, E Cimini, I Abbate, M R Capobianchi, F Martini, A Sacchi
BACKGROUND: It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. METHODS: Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled...
January 2, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28055016/inhibition-of-stat3-signaling-pathway-by-nifuroxazide-improves-antitumor-immunity-and-impairs-colorectal-carcinoma-metastasis
#10
Ting-Hong Ye, Fang-Fang Yang, Yong-Xia Zhu, Ya-Li Li, Qian Lei, Xue-Jiao Song, Yong Xia, Ying Xiong, Li-Dan Zhang, Ning-Yu Wang, Li-Feng Zhao, Hong-Feng Gou, Yong-Mei Xie, Sheng-Yong Yang, Luo-Ting Yu, Li Yang, Yu-Quan Wei
Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer target for CRC therapy. In the present study, we report our findings on nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3. Our studies showed that nifuroxazide decreased the viability of three CRC cell lines and induced apoptosis of cancer cells in a concentration-dependent manner...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28052991/myeloid-derived-suppressor-cells
#11
REVIEW
Dmitry I Gabrilovich
Myeloid cells developed evolutionarily as a major mechanism to protect the host. They evolved as a critical barrier against infections and are important contributors to tissue remodeling. However, in cancer, myeloid cells are largely converted to serve a new master-tumor cells. This process is epitomized by myeloid-derived suppressor cells (MDSC). These cells are closely related to neutrophils and monocytes. MDSCs are not present in the steady state of healthy individuals and appear in cancer and in pathologic conditions associated with chronic inflammation or stress...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28051364/the-role-of-myeloid-derived-suppressor-cells-in-viral-infection
#12
Megan A O'Connor, Jessica L Rastad, William R Green
Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells that are well described as potent immune regulatory cells during human cancer and murine tumor models. Reports of MDSCs during viral infections remain limited, and their association with immunomodulation of viral diseases is still being defined. Here, we provide an overview of MDSCs or MDSC-like cells identified during viral infections, including murine viral models and human viral diseases. Understanding the similarities and/or differences of virally induced versus tumor-derived MDSCs will be important for designing future immunotherapeutic approaches...
January 4, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28050790/first-in-human-study-of-the-antibody-dr5-agonist-ds-8273a-in-patients-with-advanced-solid-tumors
#13
Andres Forero, Johanna C Bendell, Prasanna Kumar, Linda Janisch, Michael Rosen, Qiang Wang, Catherine Copigneaux, Madhuri Desai, Giorgio Senaldi, Michael L Maitland
Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid tumors. Methods The study comprised dose escalation and dose expansion cohorts. The dose escalation cohorts intended to determine the safety and to identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) and to characterize the pharmacokinetics and pharmacodynamics by a conventional 3 + 3 design (starting at 2 mg/kg and escalating through 8, 16 and 24 mg/kg once every 3 weeks)...
January 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#14
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28031408/predictive-outcomes-for-her2-enriched-cancer-using-growth-and-metastasis-signatures-driven-by-sparc
#15
Leandro N Guttlein, Lorena G Benedetti, Cristobal Fresno, Raul G Spallanzani, Sabrina F Mansilla, Cecilia Rotondaro, Ximena L Raffo Iraolagoitia, Edgardo Salvatierra, Alicia I Bravo, Elmer A Fernandez, Vanessa Gottifredi, Norberto W Zwirner, Andrea S Llera, Osvaldo L Podhajcer
: Understanding the mechanism of metastatic dissemination is crucial for the rational design of novel therapeutics. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein which has been extensively associated with human breast cancer aggressiveness although the underlying mechanisms are still unclear. Here, shRNA-mediated SPARC knockdown greatly reduced primary tumor growth and completely abolished lung colonization of murine 4T1 and LM3 breast malignant cells implanted in syngeneic BALB/c mice...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28019655/tumor-activated-liver-stromal-cells-regulate-myeloid-derived-suppressor-cells-accumulation-in-the-liver
#16
Henghui Zhang, Gaixia He, Yaxian Kong, Yanhui Chen, Beibei Wang, Xiuyun Sun, Bei Jia, Xingwang Xie, Xueyan Wang, Dongwei Chen, Lai Wei, Minghui Zhang, Hui Zeng, Hongsong Chen
Regulating mechanisms underlying hepatic myeloid-derived suppressor cells (MDSCs) accumulation remain to be described. Here, we provide evidence for the involvement of tumor-activated liver stromal cells in the process of hepatic MDSCs migration and accumulation. Our data showed elevated frequency of MDSCs in the liver of tumor-bearing mice. Moreover, tumor-activated liver stromal cells promote MDSCs migration into the liver site. Further investigation indicated higher levels of cytokines and chemokines expression in liver stromal cells after exposure to the tumor-conditioned supernatant...
December 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#17
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28009997/myeloid%C3%A2-derived-suppressor-cells-in-bronchoalveolar-lavage-fluid-in-patients-with-chronic-obstructive-pulmonary-disease
#18
Beata Brajer-Luftmann, Agata Nowicka, Mariusz Kaczmarek, Marcin Grabicki, Barbara Kuźnar-Kamińska, Barbara Bromińska, Jan Sikora, Halina Batura-Gabryel
INTRODUCTION Myeloid‑derived suppressor cells (MDSCs) have the potent ability to suppress T‑cell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD...
December 15, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/28009291/myeloid-derived-suppressor-cells-are-controlled-by-regulatory-t-cells-via-tgf-%C3%AE-during-murine-colitis
#19
Cho-Rong Lee, Yewon Kwak, Taewoo Yang, Jung Hyun Han, Sang-Heon Park, Michael B Ye, Wongeun Lee, Kyu-Young Sim, Jung-Ah Kang, Yong-Chul Kim, Sarkis K Mazmanian, Sung-Gyoo Park
Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-β (TGF-β)...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/28008330/increased-levels-of-circulating-and-tumor-infiltrating-granulocytic-myeloid-cells-in-colorectal-cancer-patients
#20
Salman M Toor, Azharuddin Sajid Syed Khaja, Haytham El Salhat, Omar Bekdache, Jihad Kanbar, Mohammed Jaloudi, Eyad Elkord
Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment (TME) of colorectal cancer (CRC) patients, compared to blood from healthy donors (HDs) and paired, adjacent non-tumor colon tissue...
2016: Frontiers in Immunology
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