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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/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#3
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
#4
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
#5
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/29029332/identification-of-a-novel-subset-of-myeloid-derived-suppressor-cells-during-chronic-staphylococcal-infection-that-resembles-immature-eosinophils
#6
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/28993671/mdscs-are-induced-after-experimental-blunt-chest-trauma-and-subsequently-alter-antigen-specific-t-cell-responses
#7
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/28993412/il-10-release-upon-pd-1-blockade-sustains-immunosuppression-in-ovarian-cancer
#8
Purushottam Lamichhane, Lavakumar Karyampudi, Barath Shreeder, James Krempski, Deborah Bahr, Joshua Daum, Kimberly R Kalli, Ellen L Goode, Matthew S Block, Martin J Cannon, Keith L Knutson
Ligation of PD-1 in the tumor microenvironment is known to inhibit effective adaptive anti-tumor immunity. Blockade of PD-1 in humans has resulted in impressive, durable regression responses in select tumor types. However, durable responses have been elusive in ovarian cancer patients. PD-1 was recently shown to be expressed on and thereby impair the functions of tumor-infiltrating murine and human myeloid dendritic cells (TIDC) in ovarian cancer. In the present work, we characterize the regulation of PD-1 expression and the effects of PD-1 blockade on TIDC...
October 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28987474/expression-of-checkpoint-molecules-on-myeloid-derived-suppressor-cells
#9
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/28978693/myeloid-derived-suppressor-cells-inhibit-t-follicular-helper-cell-immune-response-in-japanese-encephalitis-virus-infection
#10
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
https://www.readbyqxmd.com/read/28978469/prostaglandin-e2-leads-to-the-acquisition-of-dnmt3a-dependent-tolerogenic-functions-in-human-myeloid-derived-suppressor-cells
#11
Javier Rodríguez-Ubreva, Francesc Català-Moll, Nataša Obermajer, Damiana Álvarez-Errico, Ricardo N Ramirez, Carlos Company, Roser Vento-Tormo, Gema Moreno-Bueno, Robert P Edwards, Ali Mortazavi, Pawel Kalinski, Esteban Ballestar
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28968468/irf-8-regulates-expansion-of-myeloid-derived-suppressor-cells-and-foxp3-regulatory-t-cells-and-modulates-th2-immune-responses-to-gastrointestinal-nematode-infection
#12
Rajesh M Valanparambil, Mifong Tam, Pierre-Paul Gros, Jean-Philippe Auger, Mariela Segura, Philippe Gros, Armando Jardim, Timothy G Geary, Keiko Ozato, Mary M Stevenson
Interferon regulatory factor-8 (IRF-8) is critical for Th1 cell differentiation and negatively regulates myeloid cell development including myeloid-derived suppressor cells (MDSC). MDSC expand during infection with various pathogens including the gastrointestinal (GI) nematode Heligmosomoides polygyrus bakeri (Hpb). We investigated if IRF-8 contributes to Th2 immunity to Hpb infection. Irf8 expression was down-regulated in MDSC from Hpb-infected C57BL/6 (B6) mice. IRF-8 deficient Irf8-/- and BXH-2 mice had significantly higher adult worm burdens than B6 mice after primary or challenge Hpb infection...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28963753/granulocytic-myeloid-derived-suppressor-cells-gr-mdsc-accumulate-in-cord-blood-of-preterm-infants-and-remain-elevated-during-the-neonatal-period
#13
Julian Schwarz, Vera Scheckenbach, Hellen Kugel, Bärbel Spring, Julia Pagel, Christoph Härtel, Jan Pauluschke-Fröhlich, Andreas Peter, Christian F Poets, Christian Gille, Natascha Köstlin
Preterm delivery is the leading cause of perinatal morbidity and mortality. Among the most important complications in preterm infants are peri- or postnatal infections. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells. Emerging evidence suggests that granulocytic MDSC (GR-MDSC) play a pivotal role in mediating maternal-foetal tolerance. The role of MDSC for postnatal immune-regulation in neonates is incompletely understood. Until now, nothing is known about expression of MDSC in preterm infants...
September 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28963139/pi3kgamma-activates-integrin-alpha4-and-promotes-immune-suppressive-myeloid-cell-polarization-during-tumor-progression
#14
Judith A Varner, Philippe Foubert, Megan M Kaneda
Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell-mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kgamma plays a role in regulating tumor immune suppression by promoting integrin alpha4-dependent MDSC recruitment to tumors and by stimulating the immunosuppressive polarization of MDSCs and TAMs. Here we show that integrin alpha4 promotes immunosuppressive polarization of MDSCs and TAMs downstream of PI3Kγ, thereby inhibiting antitumor immunity...
September 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28956104/daunorubicin-conjugated-with-alpha-fetoprotein-selectively-eliminates-myeloid-derived-suppressor-cells-mdscs-and-inhibits-experimental-tumor-growth
#15
Nikolai N Belyaev, Nurshat Abdolla, Yuliya V Perfilyeva, Yekaterina O Ostapchuk, Vladimir K Krasnoshtanov, Aikyn Kali, Raikhan Tleulieva
Failure of antitumor immunity in cancer was shown to be mediated by myeloid-derived suppressor cells (MDSCs), which are considered to be one of the key factors contributing to the development of malignant diseases. Therefore, the development of pharmacological approaches to effectively eliminate MDSCs in organisms carrying growing tumors is a promising pathway for potential treatment. For this purpose we propose alpha-fetoprotein (AFP) conjugated with a cytotoxic agent as a vector molecule, specifically recognizing MDSCs...
September 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28944996/negative-pressure-wound-therapy-promotes-muscle-derived-stem-cell-osteogenic-differentiation-through-mapk-pathway
#16
Hong Liu, Xun Zheng, Liang Chen, Chao Jian, Xiang Hu, Yong Zhao, Zonghuan Li, Aixi Yu
Negative pressure wound therapy (NPWT) has been revealed to be effective in the treatment of open fractures, although the underlying mechanism is not clear. This article aimed to investigate the effects of NPWT on muscle-derived stem cell (MDSC) osteoblastic differentiation and the related potential mechanism. The cell proliferation rate was substantially increased in NPWT-treated MDSCs in comparison with a static group for 3 days. There was no observable effect on the apoptosis of MDSC treated with NPWT compared with the control group for 3 days...
September 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28941055/inhibition-of-inflammatory-cytokines-and-induction-of-myeloid-derived-suppressor-cells-by-the-effects-of-granulocyte-and-monocyte-adsorption-apheresis
#17
Masanao Sakanoue, Yuko Higashi, Takuro Kanekura
Pro-inflammatory cytokines are involved in the pathogenesis of inflammatory skin diseases attributable to activated neutrophils and macrophages. Myeloid-derived suppressor cells (MDSCs) play an important role in the regulation of the immune response and possess strong immunosuppressive and anti-inflammatory properties. Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument featuring columns containing cellulose acetate (CA) beads, is designed to remove pathogenic myeloid lineage cells...
September 22, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28939663/hepatoma-intrinsic-ccrk-inhibition-diminishes-myeloid-derived-suppressor-cell-immunosuppression-and-enhances-immune-checkpoint-blockade-efficacy
#18
Jingying Zhou, Man Liu, Hanyong Sun, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, John Wong, Charing Ching Ning Chong, Paul B S Lai, Hector Kwong-Sang Wang, Shun-Wa Tsang, Tyler Goodwin, Rihe Liu, Leaf Huang, Zhiwei Chen, Joseph Jy Sung, King Lau Chow, Ka Fai To, Alfred Sze-Lok Cheng
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems...
September 22, 2017: Gut
https://www.readbyqxmd.com/read/28939082/epigenetic-therapy-regulates-the-expression-of-aldh1-and-immunologic-response-relevance-to-the-prognosis-of-oral-cancer
#19
Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
OBJECTIVES: Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS: We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28938533/trans-sialidase-based-vaccine-candidate-protects-against-trypanosoma-cruzi-infection-not-only-inducing-an-effector-immune-response-but-also-affecting-cells-with-regulatory-suppressor-phenotype
#20
Estefanía Prochetto, Carolina Roldán, Iván A Bontempi, Daiana Bertona, Luz Peverengo, Miguel H Vicco, Luz M Rodeles, Ana R Pérez, Iván S Marcipar, Gabriel Cabrera
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes...
August 29, 2017: Oncotarget
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