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Myeloid-derived suppressor cells

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https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#1
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29035909/dysregulated-myelopoiesis-and-hematopoietic-function-following-acute-physiologic-insult
#2
Tyler J Loftus, Alicia M Mohr, Lyle L Moldawer
PURPOSE OF REVIEW: The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. RECENT FINDINGS: Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term functional status...
October 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29034589/involvement-of-local-renin-angiotensin-system-in-immunosuppression-of-tumor-microenvironment
#3
Kenta Nakamura, Tomonori Yaguchi, Gaku Ohmura, Asuka Kobayashi, Naoshi Kawamura, Takashi Iwata, Yukiko Kiniwa, Ryuhei Okuyama, Yutaka Kawakami
To improve the current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSCs) which were shown to be negative factors in the immune-checkpoint blockade therapy, need to be developed. In this study, we have evaluated the role of local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Administration of angiotensin II receptor blockers (ARBs) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells...
October 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#4
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29032490/myeloid-derived-suppressor-cells-in-the%C3%A2-tumor-microenvironment-current-knowledge-and-future-perspectives
#5
REVIEW
Maria Ibáñez-Vea, Miren Zuazo, Maria Gato, Hugo Arasanz, Gonzalo Fernández-Hinojal, David Escors, Grazyna Kochan
The current knowledge on tumor-infiltrating myeloid-derived suppressor cells (MDSCs) is based mainly on the extensive work performed in murine models. Data obtained for human counterparts are generated on the basis of tumor analysis from patient samples. Both sources of information led to determination of the main suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a result of the identification of protein targets responsible for MDSCs suppressive activity, different therapeutics agents have been used to eliminate/reduce their adverse effect...
October 14, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#6
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29029545/the-role-of-toll-like-receptor-4-in-tumor-microenvironment
#7
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)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029511/mesenchymal-stromal-cells-promote-b-cell-lymphoma-in-lacrimal-glands-by-inducing-immunosuppressive-microenvironment
#8
Min Joung Lee, Se Yeon Park, Jung Hwa Ko, Hyun Ju Lee, Jin Suk Ryu, Jong Woo Park, Sang In Khwarg, Sun-Ok Yoon, Joo Youn Oh
Mesenchymal stromal cells (MSCs) have therapeutic potential for various diseases because of their anti-inflammatory and immunosuppressive properties. However, the immunosuppressive microenvironment allows tumor cells to evade immune surveillance, whereas maintenance of inflammation is required for tumor development and progression. Hence, MSCs may promote or suppress tumors in a context-dependent manner. We here investigated the effects of bone marrow-derived MSCs in a murine model of lacrimal gland B-cell lymphoma...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029332/identification-of-a-novel-subset-of-myeloid-derived-suppressor-cells-during-chronic-staphylococcal-infection-that-resembles-immature-eosinophils
#9
Oliver Goldmann, Andreas Beineke, Eva Medina
We have previously reported that myeloid-derived suppressor cells (MDSC), which are a heterogeneous population of immunosuppressive immature myeloid cells, expanded during chronic Staphylococcus aureus infection and promoted bacterial persistence by inhibiting effector T cells. Two major MDSC subsets including monocytic MDSCs (M-MDSC) and granulocytic MDSCs (G-MDSC) have been described to date. Here, we identified a new subset of MDSC (Eo-MDSC) in S. aureus-infected mice that phenotypically resembles eosinophils...
September 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29027915/a-combination-of-immune-checkpoint-inhibition-with-metronomic-chemotherapy-as-a-way-of-targeting-therapy-resistant-cancer-cells
#10
REVIEW
Irina Kareva
Therapeutic resistance remains a major obstacle in treating many cancers, particularly in advanced stages. It is likely that cytotoxic lymphocytes (CTLs) have the potential to eliminate therapy-resistant cancer cells. However, their effectiveness may be limited either by the immunosuppressive tumor microenvironment, or by immune cell death induced by cytotoxic treatments. High-frequency low-dose (also known as metronomic) chemotherapy can help improve the activity of CTLs by providing sufficient stimulation for cytotoxic immune cells without excessive depletion...
October 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29025689/soho-state-of-the-art-update-and-next-questions-biology-and-treatment-of-myelodysplastic-syndromes
#11
REVIEW
David A Sallman, Tiffany N Tanaka, Alan List, Rafael Bejar
Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by clonal hematopoiesis leading to bone marrow dysplasia and cytopenias. Recently, significant advancements have been made in understanding the pathogenic mechanisms of this disease. In particular, how a wide array of somatic mutations can induce a common clinical phenotype has been investigated. Specifically, activation of innate immune signaling (i.e. myeloid derived suppressor cells) and the NLRP3 inflammasome in hematopoietic stem/progenitor cells play a central role in the biology of MDS, leading to pyroptotic cell death and clonal expansion...
October 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28993671/mdscs-are-induced-after-experimental-blunt-chest-trauma-and-subsequently-alter-antigen-specific-t-cell-responses
#12
Yvonne Hüsecken, Sylvia Muche, Monika Kustermann, Malena Klingspor, Annette Palmer, Sonja Braumüller, Markus Huber-Lang, Klaus-Michael Debatin, Gudrun Strauss
Severe blunt chest trauma (TxT) induces a strong inflammatory response with posttraumatic immune suppression pointing to an impaired adaptive immune response. Since CD11b(+)Gr-1(+)-expressing myeloid-derived suppressor cells (MDSCs) are induced after inflammation and suppress T cell responses, MDSC induction and their impact on T cell functions was analysed in an experimental TxT model. MDSCs were induced preferentially in the lung until 24 hours after TxT. Although MDSC numbers were only faintly increased in the spleen, splenic MDSCs isolated after TxT strongly inhibited alloantigen-induced T cell proliferation in vitro...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28988508/immunological-effects-of-everolimus-in-patients-with-metastatic-renal-cell-cancer
#13
Charlotte M Huijts, Saskia J Santegoets, Tamarah D de Jong, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
The mammalian target of rapamycin (mTOR) is a crucial kinase present in all cells. Besides its role in the regulation of cell-growth, proliferation, angiogenesis, and survival of malignant tumors, mTOR additionally plays an important role in immune regulation by controlling the balance between effector T cells and regulatory T cells (Tregs). This critically affects the suppressive state of the immune system. Here, the systemic immunological effects of everolimus treatment were comprehensively investigated in five patients with metastatic renal cell cancer...
October 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28987644/considerations-for-successful-cancer-immunotherapy-in-aged-hosts
#14
REVIEW
Vincent Hurez, Álvaro Padrón, Robert S Svatek, Tyler J Curiel
Improvements in understanding cancer immunopathogenesis have now led to unprecedented successes in immunotherapy to treat numerous cancers. Although aging is the most important risk factor for cancer, most pre-clinical cancer immunotherapy studies are undertaken in young hosts. This review covers age-related immune changes as they affect cancer immune surveillance, immunopathogenesis and immune therapy responses. Declining T cell function with age can impede efficacy of age-related cancer immunotherapies, but examples of successful approaches to breach this barrier have been reported...
October 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28987474/expression-of-checkpoint-molecules-on-myeloid-derived-suppressor-cells
#15
Marlene Ballbach, Angelika Dannert, Anurag Singh, Darina M Siegmund, Rupert Handgretinger, Luca Piali, Nikolaus Rieber, Dominik Hartl
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population expanded in cancer, infection and autoimmunity capable of suppressing T-cell functions. Checkpoint inhibitors have emerged as a key therapeutic strategy in immune-oncology. While checkpoint molecules were initially associated with T cell functions, recent evidence suggests a broader expression and function in innate myeloid cells. Previous studies provided first evidence for a potential role for checkpoints on MDSCs, yet the human relevance remained poorly understood...
October 4, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28986261/mmp-9-cleaved-osteopontin-isoform-mediates-tumor-immune-escape-by-inducing-expansion-of-myeloid-derived-suppressor-cells
#16
Lijuan Shao, Bo Zhang, Lingxiong Wang, Liangliang Wu, Quancheng Kan, Kexing Fan
As an extracellular matrix protein, osteopontin (OPN) has been shown to play an important role in regulation of the immune response to tumors. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid progenitors, are major components of the immune suppressive tumor microenvironment and contribute to tumor evasion of the immune response. However, the specific regulating mechanisms underlying MDSCs expansion remain unclear. Here, we found that MDSCs accumulated in the spleen and tumors of 3LL tumor-bearing mice...
October 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28985035/tumor-associated-myeloid-cells-new-understandings-on-their-metabolic-regulation-and-their-influence-in-cancer-immunotherapy
#17
REVIEW
Chiara Porta, Antonio Sica, Elena Riboldi
Tumor-associated myeloid cells (TAMCs), mainly represented by tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), can promote tumor growth directly, by favouring tumor cell proliferation and survival, and indirectly, by creating an immunosuppressive microenvironment. Myeloid cells are characterized by an extreme phenotypical and functional plasticity. Immunometabolism is now emerging as a crucial aspect of TAMCs skewing towards pro-tumoral activities. The metabolic re-education of myeloid cells is a new strategy to boost their anti-tumor effector functions...
October 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28984471/tempering-the-clinical-effects-of-early-myeloid-derived-suppressor-cell-expansion-in-severe-sepsis-and-septic-shock
#18
Jayshil J Patel, Martin D Rosenthal, Stephen A McClave, Robert G Martindale
No abstract text is available yet for this article.
October 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28984469/reply-to-tempering-the-clinical-effects-of-early-myeloid-derived-suppressor-cell-expansion-in-severe-sepsis-and-septic-shock
#19
Fabrice Uhel, Christophe Camus, Arnaud Gacouin, Jean-Marc Tadié, Yves Le Tulzo, Mikael Roussel, Karin Tarte
No abstract text is available yet for this article.
October 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28978693/myeloid-derived-suppressor-cells-inhibit-t-follicular-helper-cell-immune-response-in-japanese-encephalitis-virus-infection
#20
Chong Wang, Nan Zhang, Luting Qi, Jiaolong Yuan, Ke Wang, Kunlun Wang, Sicong Ma, Haili Wang, Wenjuan Lou, Pingdong Hu, Muhammad Awais, Shengbo Cao, Zhen F Fu, Min Cui
Resolution of viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. In this study, we examined Japanese encephalitis virus (JEV) infection leading to acute encephalopathy depending on suppression of the adaptive immune responses mediated by innate cells. Infection with P3 strains of JEV enhanced myeloid-derived suppressor cell (MDSC) populations, and the survival rate of JEV-infected mice improved after MDSC depletion. Mechanically, P3-induced MDSCs suppressed CD4(+) T cell immune responses, especially responses of T follicular helper (Tfh) cells, leading to decreased splenic B cells (CD19(+)) and blood plasma cells (CD19(+)CD138(+)) and reduced levels of total IgM and JEV-specific neutralizing Abs...
October 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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