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https://www.readbyqxmd.com/read/28728299/-the-value-of-b7-h4-and-carcinoembryonic-antigen-in-diagnosing-the-benign-and-malignant-pleural-effusion
#1
F Wei, Y Wei, L F Li, G L Li, G J Wang
Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion...
July 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28723561/crosstalk-between-regulatory-t-cells-and-tumor-associated-dendritic-cells-negates-anti-tumor-immunity-in-pancreatic-cancer
#2
Jung-Eun Jang, Cristina H Hajdu, Caroline Liot, George Miller, Michael L Dustin, Dafna Bar-Sagi
Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on interferon-γ (IFN-γ)-producing cytotoxic CD8(+) T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c(+) dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8(+) T cell activation...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28713822/bone-marrow-mesenchymal-stem-cells-inhibit-the-function-of-dendritic-cells-by-secreting-galectin-1
#3
Yue Zhang, Xia-Hui Ge, Xue-Jun Guo, Si-Bin Guan, Xiao-Ming Li, Wen Gu, Wei-Guo Xu
This study aimed to investigate whether bone marrow-derived mesenchymal stem cells (BM-MSCs) can inhibit function of dendritic cells (DCs) by secreting Galectin-1 (Gal-1). BM-MSCs have been shown to inhibit the maturation and function of DCs, further inhibiting the activation and proliferation of T cells. However, the detailed mechanism remains unknown. In this current study, MSCs and DCs derived from mouse bone marrow were cocultured using Transwell culture plates under different in vitro conditions. The results showed that as the ratio of MSC to DC of the coculture system increased and the coculture time of the two cells prolonged, the concentrations of Gal-1, interleukin- (IL-) 10, and IL-12 in the supernatants were increased and the protein expression of Gal-1 on and within DCs was also enhanced...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28713380/targeting-the-human-t-cell-inducible-costimulator-molecule-with-a-monoclonal-antibody-prevents-graft-vs-host-disease-and-preserves-graft-vs-leukemia-in-a-xenograft-murine-model
#4
Aude Burlion, Simon Brunel, Nicolas Y Petit, Daniel Olive, Gilles Marodon
BACKGROUND: Graft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711488/immunomodulatory-intervention-with-gamma-interferon-in-mice-with-sepsis
#5
Yu Wang, Bing-Bing Kong, Wen-Ping Yang, Xin Zhao, Rong Zhang
AIMS: Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. MAIN METHODS: Male C57BL/6 mice were pretreated with recombinant human IFNg (0...
July 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/28711152/functional-analysis-of-acquired-cd28-mutations-identified-in-cutaneous-t-cell-lymphoma
#6
Grzegorz B Gmyrek, Jeanette Pingel, Jaehyuk Choi, Jonathan M Green
CD28 is the major costimulatory receptor on T cells regulating proliferation, survival and effector function. Acquired mutations in the extracellular domain of CD28 have been identified in patients with cutaneous T cell lymphoma, angioimmunoblastic T cell lymphoma and other T cell neoplasms, suggesting it may contribute to disease pathogenesis. We used a heterologous system in which mutant human CD28 was expressed on primary murine T cells deficient in CD28 to ascertain how specific mutations identified in a genetic screen of patients with cutaneous T cell lymphoma affected normal T cell function...
July 10, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28708252/redundant-and-regulatory-roles-for-tlrs-in-leishmania-infection
#7
REVIEW
Prashant Chauhan, Divanshu Shukla, Debprasad Chattopadhyay, Bhaskar Saha
Toll-like receptors (TLRs) are germ-line encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs does have far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence costimulatory molecules expression and determinant selection by MHC class-II and by MHC class-I for cross-presentation...
July 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28701870/nuclear-factor-kappa-b-and-activator-protein-1-mediated-immunostimulatory-activity-of-compound-k-in-monocytes-and-macrophages
#8
Woo Seok Yang, Young-Su Yi, Donghyun Kim, Min Ho Kim, Jae Gwang Park, Eunji Kim, Sang Yeol Lee, Keejung Yoon, Jong-Hoon Kim, Junseong Park, Jae Youl Cho
BACKGROUND: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. METHODS: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28697888/regulated-expansion-and-survival-of-chimeric-antigen-receptor-modified-t-cells-using-small-molecule-dependent-inducible-myd88-cd40
#9
Aaron E Foster, Aruna Mahendravada, Nicholas P Shinners, Wei-Chun Chang, Jeannette Crisostomo, An Lu, Mariam Khalil, Eva Morschl, Joanne L Shaw, Sunandan Saha, MyLinh T Duong, Matthew R Collinson-Pautz, David L Torres, Tania Rodriguez, Tsvetelina Pentcheva-Hoang, J Henri Bayle, Kevin M Slawin, David M Spencer
Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4(+) and CD8(+) T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function...
July 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28694293/the-trophic-life-cycle-stage-of-the-opportunistic-fungal-pathogen-pneumocystis-murina-hinders-the-ability-of-dendritic-cells-to-stimulate-cd4-t-cell-responses
#10
Heather M Evans, Andrew Simpson, Shu Shen, Arnold J Stromberg, Carol L Pickett, Beth A Garvy
The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple PAMPs, including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors...
July 10, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28679835/new-b7-family-checkpoints-in-human-cancers
#11
REVIEW
Ling Ni, Chen Dong
T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and CTL antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently, five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7, were identified...
July 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28678031/immunotherapy-based-combinations-current-status-and-perspectives
#12
María J de Miguel-Luken, André Mansinho, Valentina Boni, Emiliano Calvo
PURPOSE OF REVIEW: Since the approval of ipilimumab, different immune checkpoint inhibitors, vaccines and costimulatory agonists have been developed with success, improving patient's survival in a number of different tumour types. However, immunotherapy results in durable responses but only in a fraction of patients. In order to improve this, combination of different immune agents is currently being attempted in the clinic with the potential of becoming one day the next wave of immune treatments available for our cancer patients...
July 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28674449/dexamethasone-induced-inhibition-of-dectin-1-activation-of-antigen-presenting-cells-is-mediated-via-stat-3-and-nf-%C3%AE%C2%BAb-signaling-pathways
#13
Philipp Kotthoff, Annkristin Heine, Stefanie Andrea Erika Held, Peter Brossart
Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the production of cytokines and chemokines and T-cell stimulatory capacity of DC and mediates resolution of fungal infections. Here we show that antigen-presenting cells generated in the presence of dexamethasone (Dex-DC) have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673339/human-limbal-fibroblast-like-stem-cells-induce-immune-tolerance-in-autoreactive-t-lymphocytes-from-female-patients-with-hashimoto-s-thyroiditis
#14
Antonina Coppola, Laura Tomasello, Maria Pitrone, Salvatore Cillino, Pierina Richiusa, Giuseppe Pizzolanti, Carla Giordano
BACKGROUND: Due to their "natural immune privilege" and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto's thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients...
July 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28670716/adoptive-transfer-of-murine-t-cells-expressing-a-chimeric-pd1-dap10-receptor-as-an-immunotherapy-for-lymphoma
#15
Adam Lynch, William Hawk, Emily Nylen, Sean Ober, Pierre Autin, Amorette Barber
Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumor recognition and T cell effector functions. The PD1 receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3 zeta. Additionally, chimeric antigen receptor therapies utilize various costimulatory domains to enhance efficacy...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28657829/cd55-deficiency-early-onset-protein-losing-enteropathy-and-thrombosis
#16
Ahmet Ozen, William A Comrie, Rico C Ardy, Cecilia Domínguez Conde, Buket Dalgic, Ömer F Beser, Aaron R Morawski, Elif Karakoc-Aydiner, Engin Tutar, Safa Baris, Figen Ozcay, Nina K Serwas, Yu Zhang, Helen F Matthews, Stefania Pittaluga, Les R Folio, Aysel Unlusoy Aksu, Joshua J McElwee, Ana Krolo, Ayca Kiykim, Zeren Baris, Meltem Gulsan, Ismail Ogulur, Scott B Snapper, Roderick H J Houwen, Helen L Leavis, Deniz Ertem, Renate Kain, Sinan Sari, Tülay Erkan, Helen C Su, Kaan Boztug, Michael J Lenardo
BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance...
July 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#17
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#18
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#19
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28634588/antitumor-effect-of-kml-b-treated-dendritic-cells-via-induction-of-lymphocyte-activation
#20
Jong-Jin Kim, Yun-Ho Hwang, Kyung-Yun Kang, Sung-Ju Lee, Jong-Bae Kim, Jina Choi, Sung-Tae Yee
Lectins are carbohydrate-binding proteins with various biological activities, such as antitumor and immunomodulatory effects. Although lectins have various biological activities, they are still limited by cytotoxicity in normal cells. To overcome this problem, we used the noncytotoxic part of Korean mistletoe lectin B-chain (KML-B) to induce maturation of dendritic cells (DCs). A previous study reported that KML-B induces DC maturation by triggering TLR-4, including expression of costimulatory molecules (CD40, CD80, and CD86), MHC II, and secretion of cytokines in DCs...
2017: Journal of Immunology Research
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