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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/28733709/il-4-blockade-alters-the-tumor-microenvironment-and-augments-the-response-to-cancer-immunotherapy-in-a-mouse-model
#1
Shuku-Ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka
Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes...
July 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#2
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/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#3
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28725429/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#4
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28722681/the-role-of-toll-like-receptor-4-in-tumor-microenvironment
#5
REVIEW
Jing Li, Fan Yang, Feng Wei, Xiubao Ren
Tumors are closely related to chronic inflammation, during which there are various changes in inflammatory sites, such as immune cells infiltration, pro-inflammation cytokines production, and interaction between immune cells and tissue cells. Besides, substances, released from both tissue cells attacked by exogenous etiologies, also act on local cells. These changes induce a dynamic and complex microenvironment favorable for tumor growth, invasion, and metastasis. The toll-like receptor 4 (TLR4) is the first identified member of the toll-like receptor family that can recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMPs)...
July 8, 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
#6
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/28716080/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#7
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
July 18, 2017: Journal for Immunotherapy of Cancer
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
#8
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/28711922/hmgb1-promotes-myeloid-derived-suppressor-cells-and-renal-cell-carcinoma-immune-escape
#9
Jinfeng Li, Jiajia Sun, Ruiming Rong, Long Li, Wenjun Shang, Dongkui Song, Guiwen Feng, Feifei Luo
Despite high immunogenicity and marked presence of immune cells in the RCC(renal cell carcinoma), immunotherapy fails to develop effective anti-tumor immune responses. This is due to the negative regulatory factors in the tumor microenvironment. As the main contributor of immunosuppression, myeloid-derived suppressor cells (MDSCs) inhibited anti-tumor immunity and promoted tumor progression. Meanwhile, it is confirmed that high mobility group box-1 protein (HMGB1) shows a high expression in many solid tumors and HMGB1 with high expression is involved in tumor immune escape...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704840/hype-or-hope-the-prognostic-value-of-infiltrating-immune-cells-in-cancer
#10
Tristan A Barnes, Eitan Amir
Interactions between immune and malignant cells have been known to have clinical relevance for decades. The potential for immune control is now being therapeutically enhanced with checkpoint inhibitors and other novel agents to improve outcomes in cancer. The importance of the immune infiltrate as a prognostic marker is increasingly relevant. In this minireview, we present an overview of the immune infiltrate and its spatial organisation, and summarise the prognostic value of immune cells in different cancer types...
July 13, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28699300/angiogenic-inflammatory-and-immunologic-markers-in-predicting-response-to-sunitinib-in-metastatic-renal-cell-carcinoma
#11
Ryuichi Mizuno, Go Kimura, Satoshi Fukasawa, Takeshi Ueda, Tsunenori Kondo, Hidehiko Hara, Sunao Shoji, Kent Kanao, Hayakazu Nakazawa, Kazunari Tanabe, Shigeo Horie, Mototsugu Oya
The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyse serum angiogenic and inflammatory marker together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed...
July 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28698296/prkci-promotes-immune-suppression-in-ovarian-cancer
#12
Sharmistha Sarkar, Christopher A Bristow, Prasenjit Dey, Kunal Rai, Ruth Perets, Alejandra Ramirez-Cardenas, Shruti Malasi, Emmet Huang-Hobbs, Monika Haemmerle, Sherry Y Wu, Michael McGuire, Alexei Protopopov, Shan Jiang, Joyce F Liu, Michelle S Hirsch, Qing Chang, Alexander J Lazar, Anil K Sood, Ronny Drapkin, Ronald DePinho, Giulio Draetta, Lynda Chin
A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-ι (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration...
July 11, 2017: Genes & Development
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
#13
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/28693213/recruitment-of-cd11b-ly6c-monocytes-in-non-small-cell-lung-cancer-xenografts-challenged-by-anti-vegf-antibody
#14
Xie-Wan Chen, Jian-Guo Sun, Lu-Ping Zhang, Xing-Yun Liao, Rong-Xia Liao
A series of antibodies against vascular endothelial growth factor (VEGF) have been developed for the treatment of various types of cancer, including non-small cell lung cancer (NSCLC) in recent years. However, tumors frequently demonstrate resistance to these strategies of VEGF inhibition. Efforts to better understand the mechanism underlying the acquired resistance to anti-VEGF antibodies are warranted. In the present study, in order to develop a xenograft model of acquired resistance to anti-VEGF antibody, xenografts of human adenocarcinoma A549 cells were generated through the successive inoculation of tumor tissue explants into first (F1), second (F2) and third (F3) generations of mice treated with the anti-VEGF antibody B20...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693175/functional-analysis-of-cd14-hla-dr-low-myeloid-derived-suppressor-cells-in-patients-with-lung-squamous-cell-carcinoma
#15
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/28689360/regulatory-myeloid-cells-an-underexplored-continent-in-b-cell-lymphomas
#16
REVIEW
Mikael Roussel, Jonathan M Irish, Cedric Menard, Faustine Lhomme, Karin Tarte, Thierry Fest
In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas...
July 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28688082/circulating-myeloid-derived-suppressor-cells-increase-in-patients-undergoing-neo-adjuvant-chemotherapy-for-breast-cancer
#17
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
#18
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/28682942/protection-against-lipopolysaccharide-induced-immunosuppression-by-igg-and-igm
#19
Christiana Kyvelidou, Dimitris Sotiriou, Ioanna Zerva, Irene Athanassakis
Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the potential role of IgG and IgM in reversing LPS endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2 μg/g LPS, which was tolerable by half of the manipulated animals. Such protocol allowed longer survival, necessary in the prospect of therapeutic treatment application...
July 4, 2017: Shock
https://www.readbyqxmd.com/read/28680754/cd39-cd73-upregulation-on-myeloid-derived-suppressor-cells-via-tgf-%C3%AE-mtor-hif-1-signaling-in-patients-with-non-small-cell-lung-cancer
#20
Jieyao Li, Liping Wang, Xinfeng Chen, Lifeng Li, Yu Li, Yu Ping, Lan Huang, Dongli Yue, Zhen Zhang, Fei Wang, Feng Li, Li Yang, Jianmin Huang, Shuangning Yang, Hong Li, Xuan Zhao, Wenjie Dong, Yan Yan, Song Zhao, Bo Huang, Bin Zhang, Yi Zhang
CD39/CD73-adenosine pathway has been recently defined as an important tumor-induced immunosuppressive mechanism. We here documented a fraction of CD11b(+)CD33(+) myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor tissues from non-small cell lung cancer (NSCLC) patients expressed surface ectonucleotidases CD39 and CD73. Tumor TGF-β stimulated CD39 and CD73 expression, thereby inhibited T cell and NK cell activity, and protected tumor cells from the cytotoxic effect of chemotherapy through ectonucleotidase activity...
2017: Oncoimmunology
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