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Myeloid derived suppressor cells rat

François Huaux, Virginie d'Ursel de Bousies, Marie-Astrid Parent, Micaela Orsi, Francine Uwambayinema, Raynal Devosse, Saloua Ibouraadaten, Yousof Yakoub, Nadtha Panin, Mihaly Palmai-Pallag, Pierre van der Bruggen, Christian Bailly, Riccardo Marega, Etienne Marbaix, Dominique Lison
BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells. METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos...
2016: Particle and Fibre Toxicology
Gregory J Baker, Peter Chockley, Daniel Zamler, Maria G Castro, Pedro R Lowenstein
Malignant gliomas are resistant to natural killer (NK) cell immune surveillance. However, the mechanisms used by these cancers to suppress antitumor NK cell activity remain poorly understood. We have recently reported on a novel mechanism of innate immune evasion characterized by the overexpression of the carbohydrate-binding protein galectin-1 by both mouse and rat malignant glioma. Here, we investigate the cytokine profile of galectin-1-deficient GL26 cells and describe the process by which these tumors are targeted by the early innate immune system in RAG1(-/-) and C57BL/6J mice...
June 2016: Oncoimmunology
Z J Wang, H X Wang, L Li, L Wang, H H Dou
We investigated the influence of different fluid resuscitation techniques on the number of myeloid-derived suppressor cells (MDSCs) in rats. Seventy-two healthy Sprague-Dawley rats were randomly divided into groups that received sham operation (Sham group), hypertonic saline (HRS group), lactated ringer's solution (LRS group), or crystalloid solution (LCRS group). Six rats from each group were sacrificed by cervical dislocation at 12, 24, and 48 h after resuscitation. The spleens were harvested under sterile conditions and spleen cell suspension was prepared...
2016: Genetics and Molecular Research: GMR
E Renard, A Gaudin, G Bienvenu, J Amiaud, J C Farges, M C Cuturi, A Moreau, B Alliot-Licht
Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment...
February 2016: Journal of Dental Research
Gurcan Gunaydin, S Altug Kesikli, Dicle Guc
Circulating fibrocytes were reported to represent a novel myeloid-derived suppressor cell (MDSC) subset and they were also proposed to be involved in the tumor immune escape. This novel fibrocyte subset had a surface phenotype resembling non-monocytic MDSCs (CD14(-)CD11c(hi)CD123(-)) and exhibited immunomodulatory roles. Most effector functions of fibrocytes (circulating fibroblast-progenitors) are accomplished as tissue fibroblasts, likewise in the tumor microenvironment. Therefore, fibroblasts at tumor tissues should be evaluated whether they display similar molecular/gene expression patterns and functional roles to the blood-borne fibrocytes...
September 2015: Oncoimmunology
Yusuf Dolen, Gurcan Gunaydin, Gunes Esendagli, Dicle Guc
Limited knowledge is available on myeloid derived suppressor cells (MDSCs) of rat origin. We examined the myeloid cells from peripheral blood, bone marrow and spleens of healthy and mammary tumor bearing rats employing a novel immunophenotyping strategy with CD172a, HIS48, and Rp-1 antibodies. We addressed rat granulocytes by Rp-1 positivity and used HIS48 in discrimination of two mononuclear cell subsets. An expansion of granulocyte numbers was detected in peripheral blood and spleens of mammary tumor-bearing animals...
May 2015: Cellular Immunology
Anne Becker, Nils Große Hokamp, Stefanie Zenker, Fabian Flores-Borja, Katarzyna Barzcyk, Georg Varga, Johannes Roth, Christiane Geyer, Walter Heindel, Christoph Bremer, Thomas Vogl, Michel Eisenblaetter
UNLABELLED: Tumors recruit and reprogram immune cells to support tumor development and spread, the most prominent among them being of monocytic origin such as tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC). The alarmin S100A8/A9 has been implicated in the induction of TAM and MDSC. We assessed S100A9 as a molecular imaging marker for the activity of tumor-associated immune cells in a syngeneic murine breast cancer model. S100A9 could serve as a surrogate marker for tumor immune crosstalk as a function of malignancy, providing a tool with the potential for both basic research in tumor immunology and clinical stratification of patients...
March 2015: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Raymond N Dubois
Chronic inflammation is a risk factor for several different cancers including colorectal cancer (CRC). However, the mechanisms underlying the contribution of inflammation to cancer remain elusive. Pro-inflammatory mediators such as cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer progression. Here, we show that COX-2 is an immediate-early response gene induced by growth factors and pro-inflammatory cytokines and its levels are elevated in human CRCs. Furthermore, we show that COX-2-derived PGE2 promotes colonic tumor growth via silencing certain tumor suppressors and DNA repair genes by DNA methylation in colonic epithelial tumor cells...
2014: Transactions of the American Clinical and Climatological Association
Wei-Yu Lin, Ching Chuan Hsieh, Teng-Yao Yang, Miaw-Ling Chen, Li Ying Huang, Yi-Pai Lin, Pey-Jium Chang, Robert M Levin, Yau-Huei Wei
PURPOSE: Partial bladder outlet obstruction causes a significant increase in tissue and systemic oxidative stress markers and tissue inflammatory cytokine levels. Myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone are believed to be associated with oxidative stress and inflammation. We investigated alterations in plasma myeloid-derived suppressor cells, IFN-γ, IL-10 and aldosterone levels in partial bladder outlet obstruction and after its reversal. MATERIALS AND METHODS: Rats with surgically induced partial bladder outlet obstruction were divided into 4 groups of 3 each, including sham treated, 4-week obstruction, and 4 and 8-week obstruction with relief...
November 2014: Journal of Urology
Susumu Fujiwara, Hiroshi Nagai, Noriko Shimoura, Shuntaro Oniki, Takayuki Yoshimoto, Chikako Nishigori
Previous studies have shown that the antitumor effects of OX40 agonists depend on the immunogenicity of the tumor and that poorly immunogenic tumors such as B16F10 melanomas do not respond to OX40 agonist treatment. In this study, we have shown that intratumoral CD4+ T lymphodepletion sensitized poorly immunogenic B16F10 melanomas to immunotherapy with an OX40 agonist. CD4+ T lymphodepletion dramatically altered the tumor immune microenvironment, making it more susceptible to the antitumor effects of an OX40 agonist by enhancing the accumulation of CD8+ T cells and natural killer (NK) cells in tumor tissue...
July 2014: Journal of Investigative Dermatology
Brian R Rosborough, Dàlia Raïch-Regué, Heth R Turnquist, Angus W Thomson
Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages, regulatory dendritic cells, and myeloid-derived suppressor cells to regulate alloimmunity, their potential as cellular therapeutic agents, and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy...
February 27, 2014: Transplantation
Yuan-Qiang Lu, Lin-Hui Gu, Qin Zhang, Jiu-Kun Jiang, Han-Zhou Mou
BACKGROUND: Hemorrhagic shock is usually associated with complicated immune and inflammatory responses, which are sometimes crucial for the prognosis. As regulators of the immune and inflammatory system; proliferation, migration, distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade. METHODS: In a model of severe hemorrhagic shock, thirty-five rats were randomly divided into control, sham, normal saline resuscitation (NS), hypertonic saline resuscitation (HTS), and hydroxyethyl starch resuscitation (HES), with seven in each group...
April 2013: Chinese Medical Journal
Guang-Sheng Lei, Chen Zhang, Shoujin Shao, Hsin-Wei Jung, Pamela J Durant, Chao-Hung Lee
Pneumocystis pneumonia (PcP) develops in immunocompromised patients. Alveolar macrophages play a key role in the recognition, phagocytosis, and degradation of Pneumocystis, but their number is decreased in PcP. Our study of various inflammatory components during PcP found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with Pneumocystis pneumonia (PcP). We hypothesized that treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, may effectively control Pneumocystis (Pc) infection by inducing MDSCs to differentiate to AMs...
2013: PloS One
Chen Zhang, Guang-Sheng Lei, Shoujin Shao, Hsin-Wei Jung, Pamela J Durant, Chao-Hung Lee
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of hematopoietic precursors with the ability to adversely affect host immunity. They have been shown to accumulate in pathological conditions, such as cancer and some microbial diseases. In the mouse and rat models of Pneumocystis pneumonia (PcP), we found a distinct population of cells with MDSC-like morphology in the bronchoalveolar lavage (BAL) fluid, constituting up to 50% of the total cells in BAL fluid. These cells were not seen in the BAL fluid from normal animals or from Pneumocystis-infected animals that had been successfully treated for PcP with a combination of trimethoprim and sulfamethoxazole...
October 2012: Infection and Immunity
Nahzli Dilek, Nicolas Poirier, Claire Usal, Bernard Martinet, Gilles Blancho, Bernard Vanhove
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that are believed to inhibit immune responses in the contexts of cancer and organ transplantation, in association with regulatory T cells (Treg). However, the way in which MDSC cooperate with Treg remains elusive. In this study, we used DNA microarrays to analyze gene expression in blood-derived MDSC from rat recipients of kidney allografts. We found CCL5 (Rantes), a chemotactic C-C motif 5 chemokine, to be strongly downregulated after treatment with a tolerizing regimen...
May 1, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
Maciej Kmieciak, Debasmita Basu, Kyle K Payne, Amir Toor, Adly Yacoub, Xiang-Yang Wang, Lisa Smith, Harry D Bear, Masoud H Manjili
Attempts to cure breast cancer by adoptive cellular therapy (ACT) have not been successful. This is primarily due to the presence of tumor-induced immune-suppressive mechanisms as well as the failure of tumor-reactive T cells to provide long-term memory responses in vivo. To address these clinically important challenges, we developed an ex vivo protocol for the expansion of tumor-reactive immune cells obtained from tumor-bearing animals prior to or after local radiation therapy. We used an Ag-free protocol that included bryostatin 1/ionomycin and sequential common γ-chain cytokines (IL-7/IL-15 + IL-2)...
July 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Nahzli Dilek, Nicolas van Rompaey, Alain Le Moine, Bernard Vanhove
PURPOSE OF REVIEW: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that are considered as potential therapeutic targets. Indeed, MDSCs have been shown to suppress immune responses to several types of tumor cells and blocking their suppressive activity may adequately enhance immune response against tumor antigens. On the contrary, the activity of MDSCs may be desirable in suppressing unwanted immune responses such as allograft rejection and might be involved as non-T regulatory cells in the induction and maintenance of transplantation tolerance...
December 2010: Current Opinion in Organ Transplantation
Samuel Bertin, Tala Mohsen-Kanson, Patrick Baqué, Adolfo Gavelli, David Momier, Fabienne Anjuere, Georges F Carle, Valérie Pierrefite-Carle
Vascular endothelial growth factor is a potent pro-angiogenic growth factor which is also known to alter tumor microenvironment by inhibiting dendritic cell differentiation and promoting accumulation of myeloid-derived suppressor cells. In the present study, we analyzed the modifications induced by intratumoral expression of sFLT-1, a soluble VEGF receptor, in a rat metastatic colon carcinoma model. We generated colon cancer cell lines stably expressing sFLT-1 or a mock construct. Human umbilical vein endothelial cells cultured with conditioned medium from sFLT-1-expressing tumor cells exhibit a significantly decreased survival, demonstrating the functionality of the secreted sFLT-1...
December 8, 2010: Cancer Letters
Joseph E Burgents, Timothy P Moran, Michelle L West, Nancy L Davis, Robert E Johnston, Jonathan S Serody
We earlier showed that therapeutic vaccination of FVB/N mice with alphaviral replicon particles expressing rat neuET-VRP induced regression of established neu-expressing tumors. In this study, we evaluated the efficacy of neuET-VRPs in a tolerant mouse model using mice with transgenic expression of neu. Using the same approach that induced regression of 70 mm(2) tumors in FVB/N mice, we were unable to inhibit tumor growth in tolerant neu-N mice, despite showing neu-specific B-cell and T-cell responses post vaccination...
June 2010: Journal of Immunotherapy
Wentao Jia, Colleen Jackson-Cook, Martin R Graf
In rats bearing an intracranial T9 glioma, immunization with tumor antigens induces myeloid suppressor cells, which express neutrophil (His48) and monocyte (CD11bc) markers, to infiltrate the tumors. The His48(+)/CD11bc(+) cells were not derived from CNS microglia but were hematogenous; suppressed multiple T cell effector functions; and are myeloid-derived suppressor cells (MDSC). The glioma-infiltrating MDSC expressed arginase I, iNOS, indoleamine 2,3-dioxygenase and TGF-beta; however, inhibitor/blocking studies demonstrated that NO production was the primary mechanism of suppression which induced T cell apoptosis...
June 2010: Journal of Neuroimmunology
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