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https://www.readbyqxmd.com/read/28441391/apigenin-inhibits-tnf%C3%AE-il-1%C3%AE-induced-ccl2-release-through-ikbk-epsilon-signaling-in-mda-mb-231-human-breast-cancer-cells
#1
David Bauer, Natalie Redmon, Elizabeth Mazzio, Karam F Soliman
Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#2
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28423487/ipilimumab-treatment-decreases-monocytic-mdscs-and-increases-cd8-effector-memory-t-cells-in-long-term-survivors-with-advanced-melanoma
#3
Yago Pico de Coaña, Maria Wolodarski, Isabel Poschke, Yuya Yoshimoto, Yuan Yang, Maria Nyström, Ulrika Edbäck, Suzanne Eghyazi Brage, Andreas Lundqvist, Giuseppe V Masucci, Johan Hansson, Rolf Kiessling
Ipilimumab has revolutionized malignant melanoma therapy, but a better understanding of the mechanisms behind treatment response and adverse effects is needed. In this work, the immune system of ipilimumab treated patients was monitored to investigate potential mechanisms of action that may correlate with treatment outcome. Blood samples from 43 advanced melanoma patients were taken before, during and at the end of treatment. Hematological parameters were measured and flow cytometry analysis was performed in fresh samples within two hours of sample collection...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418921/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#4
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418913/accumulation-of-myeloid-derived-suppressor-cells-mdscs-induced-by-low-levels-of-il-6-correlates-with-poor-prognosis-in-bladder-cancer
#5
Guoliang Yang, Wenyan Shen, Yan Zhang, Mengyao Liu, Lianhua Zhang, Qiang Liu, Hui Hui Lu, Juanjie Bo
Bladder cancer (BC) is one of the most commonly occurring cancers, with a high recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here, we analyzed the markers and significance of myeloid-derived suppressor cells (MDSCs) for BC development and progression. MDSC markers were examined in peripheral blood from 113 BC patients and 20 healthy volunteers. We identified CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC patients. We also demonstrated that MDSC numbers are higher in BC patients than healthy donors, and that MDSC numbers correlate with the clinical grade, stage, and poor prognosis...
March 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#6
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414726/neem-leaf-glycoprotein-prevents-post-surgical-sarcoma-recurrence-in-swiss-mice-by-differentially-regulating-cytotoxic-t-and-myeloid-derived-suppressor-cells
#7
Madhurima Sarkar, Sarbari Ghosh, Avishek Bhuniya, Tithi Ghosh, Ipsita Guha, Subhasis Barik, Jaydip Biswas, Anamika Bose, Rathindranath Baral
Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP), a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs) was observed...
2017: PloS One
https://www.readbyqxmd.com/read/28411578/differential-effects-of-low-dose-fludarabine-or-5-fluorouracil-on-the-tumor-growth-and-myeloid-derived-immunosuppression-status-of-tumor-bearing-mice
#8
Manuchehr Abedi-Valugerdi, Wenyi Zheng, Fadwa Benkessou, Ying Zhao, Moustapha Hassan
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a key role in the suppression of the innate and adaptive immunity. Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to reduce the tumor size by depleting MDSCs. Here, we asked whether the purine analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma model, we demonstrated that in mice with advanced tumors (where MDSC-induced suppression was present), treatment with a single low-dose Flu (25, 50, 100mg/kg) elevated the numbers of splenic MDSCs and serum arginase activity, and simultaneously, increased the tumor growth (only the highest dose)...
April 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28407569/expansion-of-monocytic-myeloid-derived-suppressor-cells-in-endometriosis-patients-a-pilot-study
#9
Haiwen Chen, Shuang Qin, Aihua Lei, Xing Li, Qi Gao, Jingyin Dong, Qing Xiao, Jie Zhou
Endometriosis is a chronic inflammation disease and is closely associated with immune dysregulation. Myeloid-derived suppressor cells (MDSCs) are a negative regulator of the immune system. The aim of this study was to evaluate the possible role of MDSCs in endometriosis patients. We collected the peripheral blood and peritoneal fluid from endometriosis patients and controls and analyzed M-MDSCs level using specific monoclonal antibodies recognizing HLA-DR, CD33, CD11b, CD14 markers by flow cytometry. We found that there existed abnormal expansion of monocytic MDSCs (M-MDSCs) (HLA-DR(-/low)CD33(+)CD11b(+) CD14(+)) in peripheral blood and peritoneal fluid of patients with endometriosis...
April 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28405677/metastasized-murine-oral-squamous-cell-carcinoma-cells-induce-intratumoral-polymorphonuclear-myeloid-derived-suppressor-cells
#10
Shigeki Sumi, Naoki Umemura, Eiji Takayama, Emika Ohkoshi, Makoto Adachi, Masako Mizuno-Kamiya, Toshihiro Inagaki, Harumi Kawaki, Shinichiro Sumitomo, Nobuo Kondoh
Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28401653/selective-blockade-of-b7-h3-enhances-antitumour-immune-activity-by-reducing-immature-myeloid-cells-in-head-and-neck-squamous-cell-carcinoma
#11
Liang Mao, Teng-Fei Fan, Lei Wu, Guang-Tao Yu, Wei-Wei Deng, Lei Chen, Lin-Lin Bu, Si-Rui Ma, Bing Liu, Yansong Bian, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) promote tumour growth and metastasis by facilitating tumour transformation and angiogenesis, as well as by suppressing antitumour effector immune responses. Therefore, strategies designed to reduce MDSCs and TAMs accumulation and their activities are potentially valuable therapeutic goals. In this study, we show that negative immune checkpoint molecule B7-H3 is significantly overexpressed in human head and neck squamous cell carcinoma (HNSCC) specimen as compared with normal oral mucosa...
April 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28401258/tumor-associated-myeloid-cells-as-guiding-forces-of-cancer-cell-stemness
#12
REVIEW
Antonio Sica, Chiara Porta, Alberto Amadori, Anna Pastò
Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28400539/mass-cytometry-deep-phenotyping-of-human-mononuclear-phagocytes-and-myeloid-derived-suppressor-cells-from-human-blood-and-bone-marrow
#13
Mikael Roussel, P Brent Ferrell, Allison R Greenplate, Faustine Lhomme, Simon Le Gallou, Kirsten E Diggins, Douglas B Johnson, Jonathan M Irish
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274...
April 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28394259/a-proangiogenic-signaling-axis-in-myeloid-cells-promotes-malignant-progression-of-glioma
#14
Yujie Huang, Prajwal Rajappa, Wenhuo Hu, Caitlin Hoffman, Babacar Cisse, Joon-Hyung Kim, Emilie Gorge, Rachel Yanowitch, William Cope, Emma Vartanian, Raymond Xu, Tuo Zhang, David Pisapia, Jenny Xiang, Jason Huse, Irina Matei, Hector Peinado, Jacqueline Bromberg, Eric Holland, Bi-Sen Ding, Shahin Rafii, David Lyden, Jeffrey Greenfield
Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28389593/cxcl17-attenuates-imiquimod-induced-psoriasis-like-skin-inflammation-by-recruiting-myeloid-derived-suppressor-cells-and-regulatory-t-cells
#15
Tomonori Oka, Makoto Sugaya, Naomi Takahashi, Takehiro Takahashi, Sayaka Shibata, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato
CXCL17 is expressed in a variety of cancers and promotes tumor progression by recruiting myeloid-derived suppressor cells (MDSCs). MDSCs suppress tumor immunity by attracting regulatory T cells (Tregs) into tumor sites through CCL5. In this study, we examined the role of CXCL17 in skin disorders. CXCL17 mRNA levels in psoriasis skin, but not in lesional skin of atopic dermatitis or cutaneous T cell lymphoma, were significantly higher than those in normal skin. CXCL17 was mainly expressed in the epidermis, and IFN-γ dose-dependently increased CXCL17 expression by human keratinocytes in vitro...
April 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28383204/monocytic-myeloid-derived-suppressor-cells-regulate-t-cell-responses-against-vaccinia-virus
#16
Carl Fortin, Yiping Yang, Xiaopei Huang
Vaccinia virus (VV) can potently activate NK- and T-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid derived suppressor cells (g-MDSCs) can suppress the NK-cell response to VV infection. It remains unknown what regulates T-cell responses to VV infection in vivo. In this study, we first showed that monocytic MDSCs (m-MDSCs), but not g-MDSCs, from VV-infected mice could directly suppress CD4(+) and CD8(+) T-cell activation in vitro...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28382399/ccr5-in-recruitment-and-activation-of-myeloid-derived-suppressor-cells-in-melanoma
#17
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Using ret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment...
April 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28381543/setd1b-activates-inos-expression-in-myeloid-derived-suppressor-cells
#18
Priscilla S Redd, Mohammed Ibrahim, John D Klement, Sarah K Sharman, Amy V Paschall, Dafeng Yang, Asha Nayak-Kapoor, Kebin Liu
Inducible nitric oxide synthase (iNOS) generates nitric oxide (NO) in myeloid cells that acts as a defense mechanism to suppress invading microorganisms or neoplastic cells. In tumor-bearing mice, elevated iNOS expression is a hallmark of myeloid-derived suppressor cells (MDSC). MDSCs use NO to nitrate both the T cell receptor and STAT1, thus inhibiting T cell activation and the anti-tumor immune response. The molecular mechanisms underlying iNOS expression and regulation in tumor-induced MDSCs are unknown...
April 5, 2017: Cancer Research
https://www.readbyqxmd.com/read/28378599/liposomal-microparticle-injection-can-induce-myeloid-derived-suppressor-cells-mdsc-like-cells-in-vivo
#19
Hiroshi Azuma, Yoichiro Yoshida, Hironori Takahashi, Emi Ishibazawa, Hiroya Kobayashi, Hiromi Sakai, Daisuke Takahashi, Mitsuhiro Fujihara
CONTEXT: Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells that function as immunosuppressive cells in various pathological conditions. Membrane-derived microvesicles are thought to be involved in MDSC induction. Earlier reports have described that injection of considerable amount of liposome into rat can suppress Con A-induced splenic T-cell proliferation. Liposome-internalized cells expressing CD11b/c suppress T-cell proliferation. Nitric oxide (NO) appears to be involved in the suppression...
April 5, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28375154/type-2-innate-lymphoid-cells-treat-and-prevent-acute-gastrointestinal-graft-versus-host-disease
#20
Danny W Bruce, Heather E Stefanski, Benjamin G Vincent, Trisha A Dant, Shannon Reisdorf, Hemamalini Bommiasamy, David A Serody, Justin E Wilson, Karen P McKinnon, Warren D Shlomchik, Paul M Armistead, Jenny P Y Ting, John T Woosley, Bruce R Blazar, Dietmar M W Zaiss, Andrew N J McKenzie, James M Coghill, Jonathan S Serody
Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow...
April 4, 2017: Journal of Clinical Investigation
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