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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/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#2
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
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/28722094/-detection-and-clinical-significance-of-myeloid-derived-suppressor-cells-in-peripheral-blood-of-patients-with-rectal-carcinoma
#4
Yongchao Zhang, Jianguo Xie, Guangsen Han, Bing Dong, Yonglei Zhang, Jindai Zhang
OBJECTIVE: To study the expression of myeloid-derived suppressor cells (MDSC) in peripheral blood of patients with rectal carcinoma and to preliminarily explore its clinical significance. METHODS: Blood samples from 76 rectal carcinoma patients who underwent surgery in Department of General Surgery, The Affiliated Cancer Hospital, Zhengzhou University between June and October 2013 were collected before operation, postoperative day 10 and 2 years after operation respectively...
July 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28721630/in-situ-salification-in-polar-solvents-a-paradigm-for-enabling-drug-delivery-of-weakly-ionic-drugs-as-amorphous-solid-dispersion
#5
Rashmi Nair, Ioorika Lamare, Nirbhay Kumar Tiwari, Punna Rao Ravi, Raviraj Pillai
Solubility challenge for a poorly water-soluble drug gets further intensified when it is weakly ionic because the most common solubility enhancement technique, salt formation, becomes less feasible. Salt screening for such drugs often concludes with either a difficult to crystalize salt or an unstable salt, leading the scientists to explore other solubility enhancement technique like amorphous solid dispersions which is comparatively costlier, time-consuming and may require use of hazardous organic solvents...
July 18, 2017: AAPS PharmSciTech
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
#6
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/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/28688082/circulating-myeloid-derived-suppressor-cells-increase-in-patients-undergoing-neo-adjuvant-chemotherapy-for-breast-cancer
#9
Robert Wesolowski, Megan C Duggan, Andrew Stiff, Joseph Markowitz, Prashant Trikha, Kala M Levine, Lynn Schoenfield, Mahmoud Abdel-Rasoul, Rachel Layman, Bhuvaneswari Ramaswamy, Erin R Macrae, Maryam B Lustberg, Raquel E Reinbolt, Ewa Mrozek, John C Byrd, Michael A Caligiuri, Thomas A Mace, William E Carson Iii
This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively...
July 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28687234/myeloid-derived-suppressor-cells-modulate-b-cell-responses
#10
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...
August 2017: Immunology Letters
https://www.readbyqxmd.com/read/28680753/efficacy-of-vaccination-with-tumor-exosome-loaded-dendritic-cells-combined-with-cytotoxic-drug-treatment-in-pancreatic-cancer
#11
Li Xiao, Ulrike Erb, Kun Zhao, Thilo Hackert, Margot Zöller
Pancreatic cancer (PaCa) has a dismal prognosis and adjuvant immunotherapy frequently is of low efficacy due to immunosuppressive features of PaCa and PaCa-stroma. We here explored, whether the efficacy of vaccination with tumor-exosome (TEX)-loaded dendritic cells (DC) can be improved by combining with drugs affecting myeloid-derived suppressor cells (MDSC). Experiments were performed with the UNKC6141 PaCa line. UNKC6141 TEX-loaded DC were weekly intravenously injected, mice additionally receiving Gemcitabine (GEM) and/or ATRA and/or Sunitinib (Sun)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680747/arginase-inhibition-suppresses-lung-metastasis-in-the-4t1-breast-cancer-model-independently-of-the-immunomodulatory-and-anti-metastatic-effects-of-vegfr-2-blockade
#12
Chiara Secondini, Oriana Coquoz, Lorenzo Spagnuolo, Thibaud Spinetti, Sanam Peyvandi, Laura Ciarloni, Francesca Botta, Carole Bourquin, Curzio Rüegg
Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to anti-angiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs)...
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
#13
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/28666268/myeloid-specific-genetic-ablation-of-atp-binding-cassette-transporter-abca1-is-protective-against-cancer
#14
Maryam Zamanian-Daryoush, Daniel J Lindner, Joseph A DiDonato, Matthew Wagner, Jennifer Buffa, Patricia Rayman, John S Parks, Marit Westerterp, Alan R Tall, Stanley L Hazen
Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28666020/modulating-glioma-mediated-myeloid-derived-suppressor-cell-development-with-sulforaphane
#15
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
#16
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
#17
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/28654863/stat6-promotes-intestinal-tumorigenesis-in-a-mouse-model-of-adenomatous-polyposis-by-expansion-of-mdscs-and-inhibition-of-cytotoxic-cd8-response
#18
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/28650339/ilc2-modulated-t-cell-to-mdsc-balance-is-associated-with-bladder-cancer-recurrence
#19
Mathieu F Chevalier, Sara Trabanelli, Julien Racle, Bérengère Salomé, Valérie Cesson, Dalila Gharbi, Perrine Bohner, Sonia Domingos-Pereira, Florence Dartiguenave, Anne-Sophie Fritschi, Daniel E Speiser, Cyrill A Rentsch, David Gfeller, Patrice Jichlinski, Denise Nardelli-Haefliger, Camilla Jandus, Laurent Derré
Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2)...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28638480/mouse-ip-10-gene-delivered-by-folate-modified-chitosan-nanoparticles-and-dendritic-tumor-cells-fusion-vaccine-effectively-inhibit-the-growth-of-hepatocellular-carcinoma-in-mice
#20
Zixi Hu, Jiaojiao Chen, Sufang Zhou, Nuo Yang, Siliang Duan, Zhenghua Zhang, Jing Su, Jian He, Zhiyong Zhang, Xiaoling Lu, Yongxiang Zhao
Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells...
2017: Theranostics
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