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https://www.readbyqxmd.com/read/29166611/ccr5-directs-the-mobilization-of-cd11b-gr1-ly6c-low-polymorphonuclear-myeloid-cells-from-the-bone-marrow-to-the-blood-to-support-tumor-development
#1
Elias Hawila, Hila Razon, Gizi Wildbaum, Carolin Blattner, Yair Sapir, Yuval Shaked, Viktor Umansky, Nathan Karin
Cells of hematopoietic origin can be subdivided into cells of the lymphoid lineage and those of the myeloid lineage, among which are myeloid-derived suppressor cells (MDSCs). The MDSCs can be further divided into CD11b(+)Ly6G(-)Ly6C(hi) monocytic (Mo) MDSCs and CD11b(+)Ly6G(+)Ly6C(low) polymorphonuclear (PMN) MDSCs. Both subtypes support tumor growth and suppress anti-tumor immunity. Their accumulation at the tumor site includes mobilization from the bone marrow to the blood followed by colonization at the tumor site...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29156694/pdac-derived-exosomes-enrich-the-microenvironment-in-mdscs-in-a-smad4-dependent-manner-through-a-new-calcium-related-axis
#2
Daniela Basso, Elisa Gnatta, Andrea Padoan, Paola Fogar, Sara Furlanello, Ada Aita, Dania Bozzato, Carlo-Federico Zambon, Giorgio Arrigoni, Chiara Frasson, Cinzia Franchin, Stefania Moz, Thomas Brefort, Thomas Laufer, Filippo Navaglia, Sergio Pedrazzoli, Giuseppe Basso, Mario Plebani
Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155217/neutrophil-elastase-in-the-tumor-microenvironment
#3
Irina Lerman, Stephen R Hammes
Myeloid cell production within the bone marrow is accelerated in the setting of cancer, and the numbers of circulating and infiltrating neutrophils and granulocytic myeloid derived suppressor cells (MDSCs) correlate with tumor progression and patient survival. Cancer is therefore able to hijack the normally host-protective immune system and use it to further fuel growth and metastasis. Myeloid cells secrete neutrophil elastase and neutrophil extracellular traps (NETs) in response to cues within the tumor microenvironment, thereby leading to enhanced activity in a variety of cancer types...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29152078/cd163-as-a-novel-target-gene-of-stat3-is-a-potential-therapeutic-target-for-gastric-cancer
#4
Zhenguo Cheng, Danhua Zhang, Baocheng Gong, Pengliang Wang, Funan Liu
CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibroblasts (Cafs)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151074/interferon-lambda-2-promotes-mammary-tumor-metastasis-via-angiogenesis-extension-and-stimulation-of-cancer-cell-migration
#5
R Pingwara, K Witt-Jurkowska, K Ulewicz, J Mucha, K Tonecka, Z Pilch, B Taciak, K Zabielska-Koczywas, M Mori, S Berardozzi, B Botta, T P Rygiel, M Krol
Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-λ2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-λ2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29147615/tumor-associated-neutrophils-induce-apoptosis-of-non-activated-cd8-t-cells-in-a-tnf%C3%AE-and-no-dependent-mechanism-promoting-a-tumor-supportive-environment
#6
Janna Michaeli, Merav E Shaul, Inbal Mishalian, Avi-Hai Hovav, Liran Levy, Lidia Zolotriov, Zvi Granot, Zvi G Fridlender
The role of neutrophils in tumor progression has become in recent years a subject of growing interest. Tumor-associated neutrophils (TANs), which constitute an important portion of the tumor microenvironment, promote immunosuppression in advanced tumors by modulating the proliferation, activation and recruitment of a variety of immune cell types. Studies which investigated the consequences of manipulating TAN polarization suggest that the impact of these neutrophils on tumor progression is considerably mediated by and dependent on the presence of CD8 T-cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29142311/a-standardized-herbal-extract-mitigates-tumor-inflammation-and-augments-chemotherapy-effect-of-docetaxel-in-prostate-cancer
#7
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Yu-Chih Yang, Yi-Wen Hsiao, Mong-Hsun Tsai, Pei-Wen Hsiao
Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29139571/human-prosthetic-joint-infections-are-associated-with-myeloid-derived-suppressor-cells-mdscs-implications-for-infection-persistence
#8
Cortney E Heim, Debbie Vidlak, Jessica Odvody, Curtis W Hartman, Kevin L Garvin, Tammy Kielian
Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33(+) HLA-DR(-) CD66b(+) CD14(-/low) granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues...
November 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29137411/a-novel-polyamine-blockade-therapy-activates-an-anti-tumor-immune-response
#9
Eric T Alexander, Allyson Minton, Molly C Peters, Otto Phanstiel, Susan K Gilmour
Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4(+) and CD8(+) T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137229/activation-of-vip-signaling-enhances-immunosuppressive-effect-of-mdscs-on-cmv-induced-adaptive-immunity
#10
Parvin Forghani, Christopher T Petersen, Edmund K Waller
Vasoactive intestinal peptide (VIP) is recognized as a potent anti-inflammatory factor which affects both the innate and adaptive arms of the immune system. These effects include, but are not limited to, inhibition of T cell proliferation and disruption of immune homeostasis. Myeloid-derived suppressor cells (MDSC) are an immune regulatory cell type that has been described in settings of cancer and infectious disease._Here we demonstrate a reduced circulating monocytic MDSCs in the VIP (-/-)vs. wild type MCMV...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#11
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29132870/mtor-inhibitor-rapamycin-induce-polymorphonuclear-myeloid-derived-suppressor-cells-mobilization-and-function-in-protecting-against-acute-graft-versus-host-disease-after-bone-marrow-transplantation
#12
Yu Lin, Binsheng Wang, Wei Shan, Yamin Tan, Jingjing Feng, Lin Xu, Limengmeng Wang, Biqing Han, Mingming Zhang, Jian Yu, Xiaohong Yu, He Huang
The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) has been shown to be an effective immunosuppressor in the management of acute graft-versus-host disease (aGVHD) after bone marrow transplantation. Myeloid-derived suppressor cells (MDSCs) also have a protective effect in aGVHD regulation. However, the relationship between RAPA and MDSCs in aGVHD models is unclear. Meanwhile, the effect of RAPA on different subgroups of MDSCs is also less well described. In this study, we demonstrate that in vivo administration of RAPA results in the expansion and functional enhancement of polymorphonuclear MDSCs (PMN-MDSCs) in a murine model of aGVHD...
November 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29130057/differentiation-of-myeloid-derived-suppressor-cells-from-murine-bone-marrow-and-their-co-culture-with-splenic-dendritic-cells
#13
Giada Mondanelli, Claudia Volpi
Myeloid-derived suppressor cells (MDSCs) possess the ability to suppress the immune response, and to amplify the regulatory properties of other immune cells, i.e., dendritic cells. Here we describe a protocol in which MDSCs were differentiated from murine bone marrow cells, and CD11c(+) dendritic cells were purified from murine spleens. MDSCs and CD11c dendritic cells can be co-cultured and the immunoregulatory phenotype of the MDSCs-conditioned dendritic cells could be assessed by means of a specific functional in vivo experiment, i...
September 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29123963/blocking-c5ar-signaling-promotes-the-anti-tumor-efficacy-of-pd-1-pd-l1-blockade
#14
Haoran Zha, Xiao Han, Ying Zhu, Fei Yang, Yongsheng Li, Qijing Li, Bo Guo, Bo Zhu
Anti-PD-1/PD-L1 therapy has achieved great success in the clinic; however, only a small fraction of cancer patient benefit from PD-1/PD-L1 blockade therapy, and overcoming resistance to PD-1/PD-L1 blockade has thus become a primary priority. In this study, we demonstrated that administration of PD-1/PD-L1 antibodies resulted in the activation of the complement system and massive generation of C5a. Generation of C5a did not change the accumulation of MDSCs in either the tumor or spleen but enhanced their inhibitory potential...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29120053/tumor-conditions-induce-bone-marrow-expansion-of-granulocytic-but-not-monocytic-immunosuppressive-leukocytes-with-increased-cxcr2-expression-in-mice
#15
Zhen Bian, Lei Shi, Mahathi Venkataramani, Ahmed Mansour Abdelaal, Courtney Culpepper, Koby Kidder, Hongwei Liang, Ke Zen, Yuan Liu
Myeloid-derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor-bearing mice into four density-increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low-density granulocytes, both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T cell proliferation...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29115527/splunc1-knockout-enhances-lps-induced-lung-injury-by-increasing-recruitment-of-cd11b-gr-1-cells-to-the-spleen-of-mice
#16
Han Zhang, Xiaoling Li, Shan Liao, Heran Wang, Pan Chen, Guangchao Zhu, Yanwei Luo, Guiyuan Li, Yanhong Zhou
Short palate, lung and nasal epithelium clone 1 (SPLUNC1) is a tissue-specific gene of nasopharyngeal tissue, and has been recognized as a potential tumor-suppressor gene in nasopharyngeal carcinoma. As a secreted protein, SPLUNC1 plays an important role in innate immunity including antimicrobial and host defense. However, the related immune cells which are regulated by SPLUNC1 remain elusive. In the present study, an acute lung injury (ALI) mouse model was established by administration of lipopolysaccharide (LPS) intraperitoneal injections to wild-type and SPLUNC1-/- mice (5 mg/kg)...
November 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29109687/low-intensity-ultrasound-induced-anti-inflammatory-effects-are-mediated-by-several-new-mechanisms-including-gene-induction-immunosuppressor-cell-promotion-and-enhancement-of-exosome-biogenesis-and-docking
#17
Qian Yang, Gayani K Nanayakkara, Charles Drummer, Yu Sun, Candice Johnson, Ramon Cueto, Hangfei Fu, Ying Shao, Luqiao Wang, William Y Yang, Peng Tang, Li-Wen Liu, Shuping Ge, Xiao-Dong Zhou, Mohsin Khan, Hong Wang, Xiaofeng Yang
Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders. Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS. Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29108995/cd1d-is-a-novel-cell-surface-marker-for-human-monocytic-myeloid-derived-suppressor-cells-with-t-cell-suppression-activity-in-peripheral-blood-after-allogeneic-hematopoietic-stem-cell-transplantation
#18
Borim An, Ji-Young Lim, Suji Jeong, Dong-Mi Shin, Eun Young Choi, Chang-Ki Min, Seok-Ho Hong
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR(-)CD14(+) monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
November 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107690/effects-of-oral-and-subcutaneous-administration-of-hsp60-on-myeloid-derived-suppressor-cells-and-atherosclerosis-in-apoe-mice
#19
Yingying Hu, Zhuyue Chen, Lili Jiang, Feng Chen, Runming Jin, Longxian Cheng
HSP60 has been proved to be closely related to atherosclerosis due to its antigenicity. To determine this antigenicity effect, the ApoE-/- mice were fed with western-type diet and HSP60 was administrated orally or subcutaneously (SC) for potential vaccine against atherosclerosis. Here, we observed the ApoE-/- mice with oral HSP60 administration group showed a significant reduction in plaque size at the aortic root; accompanied by increased MSDCs (CD11b(+)Gr1(+)) in peripheral blood and spleen which was mostly composed of M-MDSCs (CD11b(+)LY6G(-)LY6C(high)), and increased plasma IL-10 and splenic Foxp3, Arg1, iNOS mRNA as well as decreased plasma IFN-γ and splenic T-bet mRNA compared to control group...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29103587/conditioned-media-from-the-renal-cell-carcinoma-cell-line-786-o-drives-human-blood-monocytes-to-a-monocytic-myeloid-derived-suppressor-cell-phenotype
#20
Shannon L Okada, Randi M Simmons, Secil Franke-Welch, Thuy H Nguyen, Alan J Korman, Stacey R Dillon, Debra G Gilbertson
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells critical in mediating immune suppression in cancer patients. To develop an in vitro assay system that functionally mimics the tumor microenvironment, we cultured human monocytes with conditioned media from several cancer cell lines. Conditioned media from five tumor cell lines induced survival and differentiation of monocytes into cells characteristically similar to macrophages and MDSCs. Notably, media from the 786.O renal cell carcinoma line induced monocytes to acquire a monocytic MDSC phenotype characterized by decreased HLA-DR expression, increased nitric oxide production, enhanced proliferation, and ability to suppress autologous CD3(+) T cell proliferation...
October 31, 2017: Cellular Immunology
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