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https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#1
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814605/adam10-mediated-icos-ligand-shedding-on-b-cells-is-necessary-for-proper-t-cell-icos-regulation-and-t-follicular-helper-responses
#2
Joseph C Lownik, Andrea J Luker, Sheela R Damle, Lauren Folgosa Cooley, Riham El Sayed, Andreas Hutloff, Costantino Pitzalis, Rebecca K Martin, Mohey Eldin M El Shikh, Daniel H Conrad
The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for maintaining proper immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that a disintegrin and metalloproteinase (ADAM)10 is the primary physiological sheddase of ICOSL in mice and humans. Using an in vivo system in which ADAM10 is deleted only on B cells, elevated levels of ICOSL were seen...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814268/the-genomic-architecture-of-mastitis-resistance-in-dairy-sheep
#3
G Banos, G Bramis, S J Bush, E L Clark, M E B McCulloch, J Smith, G Schulze, G Arsenos, D A Hume, A Psifidi
BACKGROUND: Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed...
August 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28810548/effect-of-follicular-helper-t-cells-on-the-pathogenesis-of-asthma
#4
Xiaojuan Ma, Zhan Sun, Pei Zhai, Wenyan Yu, Ting Wang, Fengsen Li, Jianbing Ding
Follicular helper T (TFH) cells are considered to be a separate T helper cell subset, specifically to help memory B cell participate in humoral immunity. It has been reported that there is an association between the imbalance of TFH function and certain autoimmune diseases. However, to the best of our knowledge, the effect of TFH cells on the process of bronchial asthma has not been investigated. The aim of the present study was to investigate the associated markers of TFH cells in bronchial asthma-induced mice...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#5
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28803728/distinct-cellular-mechanisms-underlie-anti-ctla-4-and-anti-pd-1-checkpoint-blockade
#6
Spencer C Wei, Jacob H Levine, Alexandria P Cogdill, Yang Zhao, Nana-Ama A S Anang, Miles C Andrews, Padmanee Sharma, Jing Wang, Jennifer A Wargo, Dana Pe'er, James P Allison
Immune-checkpoint blockade is able to achieve durable responses in a subset of patients; however, we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection. To address these issues, we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor-infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations...
August 9, 2017: Cell
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#7
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28775208/a-multikinase-and-dna-pk-inhibitor-combination-immunomodulates-melanomas-suppresses-tumor-progression-and-enhances-immunotherapies
#8
Alexander K Tsai, Asra Y Khan, Christina E Worgo, Lucy L Wang, Yuanyuan Liang, Eduardo Davila
Combination therapies have the potential to improve outcomes in melanoma patients but have not yet been clinically efficacious. Here, we used high-throughput flow cytometry-based screening to identify and characterize candidate therapies that might synergize with and augment T-cell immunotherapy efficacy. Two lead therapies, regorafenib and NU7441, were selected based on their ability to alter a variety of immunomodulatory proteins, including CD55, CD73, CD155, programmed death-ligand 1 (PD-L1), nerve growth factor receptor (NGFR), and HLA class I in a heterogeneous panel of melanomas...
August 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28772217/interaction-between-galectin-9-tim-3-pathway-and-follicular-helper-cd4-t-cells-contributes-to-viral-persistence-in-chronic-hepatitis-c
#9
Ya Zhuo, Yi-Fu Zhang, Hong-Jie Wu, Lei Qin, Yan-Ping Wang, A-Min Liu, Xin-Hong Wang
Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4(+) T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4(+) T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28771603/expression-of-pd-l1-and-other-immunotherapeutic-targets-in-thymic-epithelial-tumors
#10
Kathryn C Arbour, Jarushka Naidoo, Keith E Steele, Ai Ni, Andre L Moreira, Natasha Rekhtman, Paul B Robbins, Joyson Karakunnel, Andreas Rimner, James Huang, Gregory J Riely, Matthew D Hellmann
INTRODUCTION: The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs...
2017: PloS One
https://www.readbyqxmd.com/read/28766553/regulatory-t-cells-with-superior-immunosuppressive-capacity-emigrate-from-the-inflamed-colon-to-draining-lymph-nodes
#11
Y Nakanishi, R Ikebuchi, T Chtanova, Y Kusumoto, H Okuyama, T Moriya, T Honda, K Kabashima, T Watanabe, Y Sakai, M Tomura
Foxp3(+) Regulatory T cells (Tregs) play a critical role in the maintenance of colon homeostasis. Here we utilized photoconvertible KikGR mice to track immune cells from the caecum and ascending (proximal) colon in the steady state and DSS-induced colitis. We found that Tregs from the proximal colon (colonic migratory Tregs) migrated exclusively to the distal part of mesenteric lymph nodes (dMLN) in an S1PR1-dependent process. In the steady state, colonic migratory CD25(+) Tregs expressed higher levels of CD103, ICOS, LAG3 and CTLA-4 in comparison with pre-existing LN Tregs...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28748530/il-6-promotes-cd4-t-cell-and-b-cell-activation-during-plasmodium-infection
#12
Ismail Sebina, Lily G Fogg, Kylie R James, Megan S F Soon, Jasmin Akter, Bryce S Thomas, Geoffrey R Hill, Christian R Engwerda, Ashraful Haque
AIMS: Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites and protect against malaria. Studies in mice have elucidated cells and molecules driving humoral immunity to Plasmodium, including CD4(+) T-cells, B-cells, interleukin (IL)-21 and ICOS. IL-6, a cytokine readily detected in Plasmodium-infected mice and humans, is recognized in other systems as a driver of humoral immunity. Here, we examined the effect of infection-induced IL-6 on humoral immunity to Plasmodium...
July 27, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28744675/potentially-inappropriate-medication-at-hospital-admission-in-patients-with-palliative-care-needs
#13
Daniel Sevilla-Sánchez, Núria Molist-Brunet, Jordi Amblàs-Novellas, Joan Espaulella-Panicot, Carles Codina-Jané
Background Potentially inappropriate medications (PIMs) are common in older patients with polypharmacy, and are related to negative clinical results. Little information is available on the characteristics and consequences of PIMs in patients with advanced chronic conditions and palliative care needs. Objective To evaluate, for this population: (i) the prevalence of PIMs; (ii) the possible risk factors associated with its onset; and (iii) the related clinical consequences. Setting Acute-hospital care Geriatric Unit (AGU) in County of Osona, Spain...
July 25, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28741317/significantly-enhanced-hydrogen-evolution-activity-of-freestanding-pd-ru-distorted-icosahedral-clusters-with-less-than-600-atoms
#14
Zhihui Dai, Suli Liu, Qinghua Zhang, Jianchun Bao, Yafei Li, Lin Gu
Freestanding metal nanoclusters can tune, precisely and effectively, the Gibbs free energy (ΔGH) of atomic hydrogen on the surface of materials. This enables the enhancement of hydrogen evolution activity. In this paper, we report a study of freestanding Pd-Ru distorted icosahedral clusters (ico-clusters) with less than 600 atoms using a simple one-pot synthesis method. This Pd-Ru ico-cluster can be used as an efficient electrocatalyst for the hydrogen evolution reaction (HER) in acidic water, which is a promising alternative to Pt...
July 24, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28728856/achaete-scute-complex-homologue-2-accelerates-the-development-of-sj%C3%A3-gren-s-syndrome-like-disease-in-the-nod-shiltj-mouse
#15
Sung-Min Kim, Jeong-Eun Kwon, Jin-Sil Park, Hyeon-Beom Seo, Kyung-Ah Jung, Young-Mee Moon, Jennifer Lee, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park
Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28719416/the-ophthalmology-surgical-competency-assessment-rubric-for-trabeculectomy
#16
Catherine M Green, Sarwat Salim, Deepak P Edward, Raghu C Mudumbai, Karl Golnik
PURPOSE: To produce an internationally valid tool to assess skill in performing trabeculectomy surgery. METHODS: A panel of 5 experts developed a tool for assessing trabeculectomy surgery by using a modified Dreyfus scale of skill acquisition and providing descriptors for each level of skill for each category. The tool was then reviewed by a panel of 10 international content experts for their constructive comments, which were incorporated into the final rubric tool...
July 17, 2017: Journal of Glaucoma
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
#17
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/28700710/t-follicular-helper-cells-regulate-the-activation-of-b-lymphocytes-and-antibody-production-during-plasmodium-vivax-infection
#18
Maria Marta Figueiredo, Pedro Augusto Carvalho Costa, Suelen Queiroz Diniz, Priscilla Miranda Henriques, Flora Satiko Kano, Mauro Sugiro Tada, Dhelio Batista Pereira, Irene Silva Soares, Olindo Assis Martins-Filho, Dragana Jankovic, Ricardo Tostes Gazzinelli, Lis Ribeiro do Valle Antonelli
Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh cells, interleukin (IL) 21 production and robust germinal center formation are associated with protection against malaria in mice, whether Tfh cells are found during Plasmodium vivax (P. vivax) infection and if they play a role during disease remains unknown...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28692472/quantification-of-immune-dysregulation-by-next-generation-polymerase-chain-reaction-to-improve-sepsis-diagnosis-in-surgical-patients
#19
Raquel Almansa, Alicia Ortega, Ana Ávila-Alonso, Maria Heredia-Rodríguez, Silvia Martín, Diana Benavides, Marta Martín-Fernandez, Lucia Rico, César Aldecoa, Jesús Rico, Iñigo López de Cenarruzabeitia, Juan Beltrán de Heredia, Esther Gomez-Sanchez, Marta Aragón, Cristina Andrés, Dolores Calvo, David Andaluz-Ojeda, Pilar Liu, Francisco Blanco-Antona, Lydia Blanco, Jose Ignacio Gómez-Herreras, Eduardo Tamayo, Jesus F Bermejo-Martin
OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28687069/%C3%AE-%C3%AE-tfh-cells-promote-b-cell-maturation-and-antibody-production-in-neuroblastoma
#20
Wenjun Mou, Wei Han, Xiaoli Ma, Xiaolin Wang, Hong Qin, Wen Zhao, Xiaoya Ren, Xi Chen, Wei Yang, Haiyan Cheng, Xisi Wang, Hui Zhang, Xin Ni, Huanmin Wang, Jingang Gui
BACKGROUND: Previous studies have shown that γδ TFH cells are capable of modulating antibody production in immunized and infected mouse model. In recent studies, human γδ TFH cells are shown to contribute to the activation of humoral immunity and promote the maturation of B cells. However, little information is available on their involvement in neuroblastoma (NB) pathogenesis. RESULTS: In the present study, the frequency of γδ TFH cells in 74 NB patients was significantly higher compared with that in 60 healthy controls...
July 7, 2017: BMC Immunology
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