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https://www.readbyqxmd.com/read/29352050/lxr-agonism-depletes-mdscs-to-promote-antitumor-immunity
#1
(no author information available yet)
LXR activation reduces immunosuppressive MDSCs to activate antitumor cytotoxic T cells.
January 19, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29348500/myeloid-derived-suppressor-cells-coming-of-age
#2
REVIEW
Filippo Veglia, Michela Perego, Dmitry Gabrilovich
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathologic conditions ranging from cancer to obesity. These cells represent a pathologic state of activation of monocytes and relatively immature neutrophils. MDSCs are characterized by a distinct set of genomic and biochemical features, and can, on the basis of recent findings, be distinguished by specific surface molecules. The salient feature of these cells is their ability to inhibit T cell function and thus contribute to the pathogenesis of various diseases...
January 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29345064/tlr8-ligation-induces-apoptosis-of-monocytic-myeloid-derived-suppressor-cells
#3
Yushe Dang, Zina J Rutnam, Gregory Dietsch, Hailing Lu, Yi Yang, Robert Hershberg, Mary L Disis
Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral blood of cancer patients and demonstrate cancer-promoting activity across multiple tumor types. A limited number of agents are known to impact MDSC activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8 on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the levels of mMDSC in volunteers and cancer donors versus control (P < 0...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29340089/lncrna-rncr3-promotes-chop-expression-by-sponging-mir-185-5p-during-mdsc-differentiation
#4
Wencong Shang, Zhenzhen Tang, Yunhuan Gao, Houbao Qi, Xiaomin Su, Yuan Zhang, Rongcun Yang
Myeloid-derived suppressor cells (MDSCs) play a critical role in regulating immune responses in cancer and other pathological conditions. Mechanism(s) regulating MDSC differentiation and function is not completely clear, especially epigenetic regulation. In this study, we found that MDSCs express retinal non-coding RNA3 (RNCR3), and the expression in MDSCs is upregulated by inflammatory and tumor associated factors. RNCR3 may function as a competing endogenous RNA (ceRNA) to promote Chop expression by sponging miR-185-5p during MDSC differentiation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#5
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29337259/mathematical-modeling-of-tumor-induced-immunosuppression-by-myeloid-derived-suppressor-cells-implications-for-therapeutic-targeting-strategies
#6
Seyed Peyman Shariatpanahi, Seyed Pooya Shariatpanahi, Keivan Madjidzadeh, Moustapha Hassan, Manuchehr Abedi-Valugerdi
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29336888/lxr-apoe-activation-restricts-innate-immune-suppression-in-cancer
#7
Masoud F Tavazoie, Ilana Pollack, Raissa Tanqueco, Benjamin N Ostendorf, Bernardo S Reis, Foster C Gonsalves, Isabel Kurth, Celia Andreu-Agullo, Mark L Derbyshire, Jessica Posada, Shugaku Takeda, Kimia N Tafreshian, Eric Rowinsky, Michael Szarek, Roger J Waltzman, Elizabeth A Mcmillan, Connie Zhao, Monica Mita, Alain Mita, Bartosz Chmielowski, Michael A Postow, Antoni Ribas, Daniel Mucida, Sohail F Tavazoie
Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial...
January 9, 2018: Cell
https://www.readbyqxmd.com/read/29334374/transitory-presence-of-myeloid-derived-suppressor-cells-in-neonates-is-critical-for-control-of-inflammation
#8
Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331939/volumetric-muscle-loss-injury-repair-using-in-situ-fibrin-gel-cast-seeded-with-muscle-derived-stem-cells-mdscs
#9
Nadine Matthias, Samuel D Hunt, Jianbo Wu, Jonathan Lo, Laura A Smith Callahan, Yong Li, Johnny Huard, Radbod Darabi
Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting...
January 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#10
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29322091/a-retroviral-replicating-vector-encoding-cytosine-deaminase-and-5-fc-induces-immune-memory-in-metastatic-colorectal-cancer-models
#11
Kader Yagiz, Maria E Rodriguez-Aguirre, Fernando Lopez Espinoza, Tiffany T Montellano, Daniel Mendoza, Leah A Mitchell, Carlos E Ibanez, Noriyuki Kasahara, Harry E Gruber, Douglas J Jolly, Joan M Robbins
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls...
March 30, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#12
Yu Ren, Hefei Wang, Si Ha, Xingsheng Zhao, Xiao Wang, Yu Lan, Xiaoling Liu
Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#13
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311360/myeloid-derived-suppressor-cells-mediate-inflammation-resolution-in-humans-and-mice-with-autoimmune-uveoretinitis
#14
Hyun Jeong Jeong, Hyun Ju Lee, Jung Hwa Ko, Bum-Joo Cho, Se Yeon Park, Jong Woo Park, Se Rang Choi, Jang Won Heo, Sun-Ok Yoon, Joo Youn Oh
Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DR-CD11b+CD33+CD14+ human MDSCs and CD11b+Ly6G-Ly6C+ mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306019/sirt1-and-hif1%C3%AE-signaling-in-metabolism-and-immune-responses
#15
Qing Yu, Lin Dong, Yan Li, Gaungwei Liu
SIRT1 and HIF1α are regarded as two key metabolic sensors in cellular metabolism pathways and play vital roles in influencing immune responses. SIRT1 and HIF1α regulate immune responses in metabolism-dependent and -independent ways. Here, we summarized the recent knowledge of SIRT1 and HIF1α signaling in metabolism and immune responses. HIF1α is a direct target of SIRT1. Sometimes, SIRT1 and HIF1α cooperate or act separately to mediate immune responses. In innate immune responses, SIRT1 can regulate the glycolytic activity of myeloid-derived suppressor cells (MDSCs) and influence MDSC functional differentiation...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29301578/notch1-signaling-in-melanoma-cells-promoted-tumor-induced-immunosuppression-via-upregulation-of-tgf-%C3%AE-1
#16
Zike Yang, Yanxia Qi, Nan Lai, Jiahe Zhang, Zehong Chen, Mingyu Liu, Wan Zhang, Rongcheng Luo, Shijun Kang
BACKGROUND: The receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells. METHODS: Melanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice...
January 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29301364/immune-evasion-in-pancreatic-cancer-from-mechanisms-to-therapy
#17
REVIEW
Neus Martinez-Bosch, Judith Vinaixa, Pilar Navarro
Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, remains one of the most challenging problems for the biomedical and clinical fields, with abysmal survival rates and poor therapy efficiency. Desmoplasia, which is abundant in PDA, can be blamed for much of the mechanisms behind poor drug performance, as it is the main source of the cytokines and chemokines that orchestrate rapid and silent tumor progression to allow tumor cells to be isolated into an extensive fibrotic reaction, which results in inefficient drug delivery...
January 3, 2018: Cancers
https://www.readbyqxmd.com/read/29296839/pak2-regulates-myeloid-derived-suppressor-cell-development-in-mice
#18
Yi Zeng, Seongmin Hahn, Jessica Stokes, Emely A Hoffman, Monika Schmelz, Maria Proytcheva, Jonathan Chernoff, Emmanuel Katsanis
Myeloid-derived suppressor cells (MDSCs) are CD11b+Gr1+ cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11bhighGr1high cells in mice. In this study, we confirmed that Pak2-KO CD11bhighGr1high cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4+ T cells that produced more interferon γ, tumor necrosis factor α, and GM-CSF...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291452/ifn-%C3%AE-decreased-the-suppressive-function-of-cd33-hla-drlow-myeloid-cells-through-down-regulation-of-pd-1-pd-l2-signaling-pathway
#19
Xiaoxia Zhan, Shengfeng Hu, Yongjian Wu, Miao Li, Ting Liu, Siqi Ming, Minhao Wu, Min Liu, Xi Huang
Myeloid-derived suppressor cells (MDSCs) have recently been described to inhibit protective T-cell responses in tuberculosis (TB). T cells play an important role in the immunity to Mycobacterium tuberculosis, and are the major producers of IFN-γ. However, the impact of IFN-γ on MDSCs during TB is still not completely understood. Our study demonstrated a significant correlation between MDSC levels and TB progression, suggesting that MDSCs may serve as a potential marker in diagnosis or treatment of TB. Culture with GM-csf and IL-6 promoted peripheral blood mononuclear cells (PBMCs) to differentiate into functional CD33+HLA-DRlow MDSC-like cells...
December 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29290791/a-novel-dna-aptamer-for-dual-targeting-of-polymorphonuclear-myeloid-derived-suppressor-cells-and-tumor-cells
#20
Haoran Liu, Junhua Mai, Jianliang Shen, Joy Wolfram, Zhaoqi Li, Guodong Zhang, Rong Xu, Yan Li, Chaofeng Mu, Youli Zu, Xin Li, Ganesh L Lokesh, Varatharasa Thiviyanathan, David E Volk, David G Gorenstein, Mauro Ferrari, Zhongbo Hu, Haifa Shen
Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. Methods: In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through in vivo selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin. Results: T1 exhibited a high affinity for both tumor cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs)...
2018: Theranostics
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