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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#1
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211355/correction-cpg-blocks-immunosuppression-by-myeloid-derived-suppressor-cells-in-tumor-bearing-mice
#2
(no author information available yet)
No abstract text is available yet for this article.
February 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28205614/cxcr2-deficient-mice-display-macrophage-dependent-exaggerated-acute-inflammatory-responses
#3
Douglas P Dyer, Kenneth Pallas, Laura Medina Ruiz, Fabian Schuette, Gillian J Wilson, Gerard J Graham
CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#4
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#5
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#6
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#7
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193828/epigenetic-component-p66a-modulates-myeloid-derived-suppressor-cells-by-modifying-stat3
#8
Jiaxuan Xin, Zhiqian Zhang, Xiaomin Su, Liyang Wang, Yuan Zhang, Rongcun Yang
STAT3 plays a critical role in myeloid-derived suppressor cell (MDSC) accumulation and activation. Most studies have probed underlying mechanisms of STAT3 activation. However, epigenetic events involved in STAT3 activation are poorly understood. In this study, we identified several epigenetic-associated proteins such as p66a (Gatad2a), a novel protein transcriptional repressor that might interact with STAT3 in functional MDSCs, by using immunoprecipitation and mass spectrometry. p66a could regulate the phosphorylation and ubiquitination of STAT3...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28193698/the-innate-and-adaptive-infiltrating-immune-systems-as-targets-for-breast-cancer-immunotherapy
#9
Andrew Mk Law, Elgene Lim, Christopher Ormandy, David Gallego-Ortega
A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis, and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy...
February 13, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28192720/dendritic-cells-in-cancer-the-role-revisited
#10
REVIEW
Filippo Veglia, Dmitry I Gabrilovich
Dendritic cells (DCs) with their potent antigen presenting ability are long considered as critical factor in antitumor immunity. Despite high potential in promoting antitumor responses, tumor-associated DCs are largely defective in their functional activity and can contribute to immune suppression in cancer. In recent years existence of immune suppressive regulatory DCs in tumor microenvironment was described. Monocytic myeloid derived suppressor cells (M-MDSCs) can contribute to the pool of tumor associated DCs by differentiating to inflammatory DCs (inf-DCs), which appear to have specific phenotype and is critical component of antitumor response...
February 10, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28191010/role-of-dietary-metabolites-in-regulating-the-host-immune-response-in-gastrointestinal-disease
#11
REVIEW
Mohamad El-Zaatari, John Y Kao
The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28187313/il-20-contributes-to-low-grade-inflammation-and-weight-gain-in-the-psammomys-obesus
#12
Helena Cucak, Lise Høj Thomsen, Alexander Rosendahl
The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To determine the importance of inflammation in obesity and diabetes, in a normal non-genetically modified species, an intervention study with neutralizing anti-IL-20 antibodies was conducted in the spontaneous T2D model Psammomys obesus. All IL-20 receptor chains were expressed on protein level in the Psammomys obesus. Neutralization of IL-20 did not modulate blood glucose, HbA1c, insulin levels or lymphocyte numbers after five weeks treatment although a trend to reduced weight gain rate was observed upon anti-IL-20 treatment...
February 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28186976/32-phosphorus-selectively-delivered-by-listeria-to-pancreatic-cancer-demonstrates-a-strong-therapeutic-effect
#13
Dinesh Chandra, Benson Chellakkan Selvanesan, Ziqiang Yuan, Steven K Libutti, Wade Koba, Amanda Beck, Kun Zhu, Arturo Casadevall, Ekaterina Dadachova, Claudia Gravekamp
Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186730/engineered-hydrogen-bonded-glycopolymer-capsules-and-their-interactions-with-antigen-presenting-cells
#14
Kristian Kempe, Sue D Xiang, Paul Wilson, Md Arifur Rahim, Yi Ju, Michael R Whittaker, David M Haddleton, Magdalena Plebanski, Frank Caruso, Thomas P Davis
Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)...
February 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28179538/the-clinical-evidence-for-targeting-human-myeloid-derived-suppressor-cells-in-cancer-patients
#15
REVIEW
Richard P Tobin, Dana Davis, Kimberly R Jordan, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that represent a formidable obstacle to the successful treatment of cancer. Patients with high frequencies of MDSCs have significantly decreased progression-free survival (PFS) and overall survival (OS). Whereas there is experimental evidence that the reduction of the number and/or suppressive function of MDSCs in mice improves the efficacy of anti-cancer therapies, there is notably less evidence for this therapeutic strategy in human clinical trials...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28178645/surgery-induced-monocytic-myeloid-derived-suppressor-cells-expand-regulatory-t-cells-in-lung-cancer
#16
Jun Wang, Liu Yang, Lu Yu, Yi-Yin Wang, Rui Chen, Jing Qian, Zhi-Peng Hong, Xiao-San Su
While monocytic myeloid-derived suppressor cells (M-MDSCs) have been reported to induce the development of regulatory T cells (Treg), little is known about their correlation with Treg during perioperative period. Here, we demonstrated that the M-MDSCs expressing CD11b+CD33+HLA-DR-CD14+ in lung cancer patients after thoractomy significantly increased in comparison with preoperation, and their accumulation linearly correlated with an increase in Treg. Surgery-induced M-MDSCs, in addition to have high arginase activity, were more efficient in suppressing T-cell proliferation...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28168165/innate-immune-pathways-associated-with-lung-radioprotection-by-soy-isoflavones
#17
Lisa M Abernathy, Matthew D Fountain, Michael C Joiner, Gilda G Hillman
INTRODUCTION: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radioprotection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury. METHODS: BALB/c mice (5-6 weeks old) received a single 10 Gy dose of thoracic irradiation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28167668/myeloid-specific-knockout-of-nfi-a-improves-sepsis-survival
#18
Melissa B McPeak, Dima Youssef, Danielle A Williams, Christopher Pritchett, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Myeloid-derived suppressor cells (MDSCs) arise from myeloid progenitors and suppress both innate and adaptive immunity. MDSCs expand during the later phases of sepsis in mice, promote immunosuppression, and reduce survival. Here, we report that the myeloid differentiation-related transcription factor NFI-A controls MDSC expansion during sepsis and impacts survival. Unlike MDSCs, myeloid cells with conditional deletion of the Nfia normally differentiated into effector cells during sepsis, cleared infecting bacteria, and did not express immunosuppressive mediators...
February 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28166447/nutrition-support-for-persistent-inflammation-immunosuppression-and-catabolism-syndrome
#19
Frederick A Moore, Stuart Phillips, Craig McClain, Jayshil J Patel, Robert Martindale
Despite tremendous advances in critical care, multiple-organ failure continues to be a significant problem. However, in recent years, far fewer patients with multiple-organ failure die early, but many experience ongoing immune dysregulation and are developing persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most PICS patients are discharged to nonhome destinations, fail to rehabilitate, and succumb to indolent death. From a nutrition perspective, patients with PICS experience persistent inflammation-induced cachexia despite evidenced-based recommended intensive care unit nutrition support...
February 1, 2017: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/28159935/lncrnas-as-an-intermediate-in-hpv16-promoting-myeloid-derived-suppressor-cell-recruitment-of-head-and-neck-squamous-cell-carcinoma
#20
Xiangrui Ma, Surui Sheng, Jingbiao Wu, Yaping Jiang, Xiaolei Gao, Xiao Cen, Jiashun Wu, Shasha Wang, Yajie Tang, Yaling Tang, Xinhua Liang
The emerging evidence showed that long noncoding RNAs (lncRNAs) are involved in cell growth and apoptosis as well as cancer progression and metastasis of malignant tumor, however, limited data are available on the role of lncRNAs in human papillomavirus (HPV)-associated Head and neck squamous cell carcinomas (HNSCC). Here, we demonstrated that 23.98% of 196 HNSCC cases in Southwest China could be classified as HPV16 infection. The number of MDSCs in HPV-positive HNSCC was significantly higher than normal control, indicating that HPV infection may promote MDSCs aggregation...
February 1, 2017: Oncotarget
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