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https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#1
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635590/imbalance-between-innate-antiviral-and-pro-inflammatory-immune-responses-may-contribute-to-different-outcomes-involving-low-and-highly-pathogenic-avian-influenza-h5n3-infections-in-chickens
#2
John Pasick, Sandra Diederich, Yohannes Berhane, Carissa Embury-Hyatt, Wanhong Xu
In order to gain further insight into the early virus-host interactions associated with highly pathogenic avian influenza virus infections in chickens, genome-wide expression profiling of chicken lung and brain was carried out at 24 and 72 h post-inoculation (h p.i.). For this purpose two recombinant H5N3 viruses were utilized, each possessing a polybasic HA0 cleavage site but differing in pathogenicity. The original rH5N3 P0 virus, which has a low-pathogenic phenotype, was passaged six times through chickens to give rise to the derivative rH5N3 P6 virus, which is highly pathogenic (Diederich S, Berhane Y, Embury-Hyatt C, Hisanaga T, Handel K et al...
June 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28635517/a-primer-for-oncoimmunology-immunooncology
#3
Brad Bolon, Famke Aeffner
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28634643/acute-high-caffeine-exposure-increases-autophagic-flux-and-reduces-protein-synthesis-in-c2c12-skeletal-myotubes
#4
M A Hughes, R M Downs, G W Webb, C L Crocker, S T Kinsey, Bradley L Baumgarner
Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux...
June 20, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#5
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634588/antitumor-effect-of-kml-b-treated-dendritic-cells-via-induction-of-lymphocyte-activation
#6
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
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#7
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634471/a-chitin-binding-protein-purified-from-moringa-oleifera-seeds-presents-anticandidal-activity-by-increasing-cell-membrane-permeability-and-reactive-oxygen-species-production
#8
João X S Neto, Mirella L Pereira, Jose T A Oliveira, Lady C B Rocha-Bezerra, Tiago D P Lopes, Helen P S Costa, Daniele O B Sousa, Bruno A M Rocha, Thalles B Grangeiro, José E C Freire, Ana Cristina O Monteiro-Moreira, Marina D P Lobo, Raimunda S N Brilhante, Ilka M Vasconcelos
Candida species are opportunistic pathogens that infect immunocompromised and/or immunosuppressed patients, particularly in hospital facilities, that besides representing a significant threat to health increase the risk of mortality. Apart from echinocandins and triazoles, which are well tolerated, most of the antifungal drugs used for candidiasis treatment can cause side effects and lead to the development of resistant strains. A promising alternative to the conventional treatments is the use of plant proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634419/elevated-plasma-levels-of-sil-2r-in-complex-regional-pain-syndrome-a-pathogenic-role-for-t-lymphocytes
#9
Krishna D Bharwani, Maaike Dirckx, Dirk L Stronks, Willem A Dik, Marco W J Schreurs, Frank J P M Huygen
The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 - Q1 = 5731 pg/ml - 3546 pg/ml) versus 1907 pg/ml (Q3 - Q1: 2206 pg/ml - 1374 pg/ml), p < 0...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634298/analyses-of-pde-regulated-phosphoproteomes-reveal-unique-and-specific-camp-signaling-modules-in-t-cells
#10
Michael-Claude G Beltejar, Ho-Tak Lau, Martin G Golkowski, Shao-En Ong, Joseph A Beavo
Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches using subcellularly targeted FRET reporter sensors have helped define more compartmentalized regulation of cAMP, PKA, and EPAC, they have limited ability to link this regulation to downstream effector molecules and biological functions...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#11
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#12
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634224/igh-myc-translocation-associates-with-brca2-deficiency-and-synthetic-lethality-to-parp1-inhibitors
#13
Silvia Maifrede, Kayla Martin, Paulina Podszywalow-Bartnicka, Katherine Sullivan, Samantha K Langer, Reza Nejadi, Yashodhara Dasgupta, Michael Hulse, Daniel Gritsyuk, Margaret Nieborowska-Skorska, Lena N Lupey-Green, Huaqing Zhao, Katarzyna Piwocka, Mariusz A Wasik, Italo Tempera, Tomasz Skorski
Burkitt lymphoma/leukemia (BL) cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of the MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive BL cells accumulate a high number of potentially lethal DNA double-strand breaks (DSBs) and display low levels of the BRCA2 tumor suppressor protein, which is a key element of homologous recombination (HR)-mediated DSB repair. BRCA2 deficiency in IGH/MYC-positive cells was associated with diminished HR activity and hypersensitivity to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors (olaparib, talazoparib) used alone or in combination with cytarabine in vitro...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#14
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634161/oncolytic-adenovirus-expressing-bispecific-antibody-targets-t-cell-cytotoxicity-in-cancer-biopsies
#15
Joshua D Freedman, Joachim Hagel, Eleanor M Scott, Ioannis Psallidas, Avinash Gupta, Laura Spiers, Paul Miller, Nikolaos Kanellakis, Rebecca Ashfield, Kerry D Fisher, Margaret R Duffy, Leonard W Seymour
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single-chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T-cell engager (BiTE) binds to EpCAM on target cells and cross-links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication...
June 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28634033/nickel-sulfate-promotes-il-17a-producing-cd4-t-cells-by-an-il-23-dependent-mechanism-regulated-by-tlr4-and-jak-stat-pathways
#16
Rami Bechara, Diane Antonios, Hayat Azouri, Marc Pallardy
Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. While IL-12p70 promotes T helper (Th) 1 cells polarization, IL-23 promotes Th17 cells development and both have been isolated from nickel-allergic patients. In this work, we were interested in understanding the mechanism behind nickel-induced Th17 cells development...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634018/distribution-subtype-population-and-ige-positivity-of-mast-cells-in-chronic-rhinosinusitis-with-nasal-polyps
#17
Shintaro Baba, Kenji Kondo, Maho Suzukawa, Ken Ohta, Tatsuya Yamasoba
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been categorized into 2 subtypes in the Asian population: eosinophilic chronic rhinosinusitis (ECRS; similar to CRSwNP in Western countries) and non-ECRS (characterized by inflammation dominated by T-helper cell type 1). The pathogenesis of CRSwNP and the role of mast cells are poorly understood. OBJECTIVE: To investigate the distribution, phenotypes, and immunoglobulin E (IgE) positivity of mast cells in these 2 subtypes of CRSwNP...
June 17, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#18
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633655/inhibition-of-mmp-2-and-mmp-9-decreases-cellular-migration-and-angiogenesis-in-in-vitro-models-of-retinoblastoma
#19
Anderson H Webb, Bradley T Gao, Zachary K Goldsmith, Andrew S Irvine, Nabil Saleh, Ryan P Lee, Justin B Lendermon, Rajini Bheemreddy, Qiuhua Zhang, Rachel C Brennan, Dianna Johnson, Jena J Steinle, Matthew W Wilson, Vanessa M Morales-Tirado
BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633645/generation-of-populations-of-antigen-specific-cytotoxic-t-cells-using-dcs-transfected-with-dna-construct-encoding-her2-neu-tumor-antigen-epitopes
#20
Maria Kuznetsova, Julia Lopatnikova, Julia Khantakova, Rinat Maksyutov, Amir Maksyutov, Sergey Sennikov
BACKGROUND: Recent fundamental and clinical studies have confirmed the effectiveness of utilizing the potential of the immune system to remove tumor cells disseminated in a patient's body. Cytotoxic T lymphocytes (CTLs) are considered the main effectors in cell-mediated antitumor immunity. Approaches based on antigen presentation to CTLs by dendritic cells (DCs) are currently being intensively studied, because DCs are more efficient in tumor antigen presentation to T cells through their initiation of strong specific antitumor immune responses than other types of antigen-presenting cells...
June 20, 2017: BMC Immunology
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