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https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#1
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#2
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28530838/an-innovative-high-throughput-screening-approach-for-discovery-of-small-molecules-that-inhibit-tnf-receptors
#3
Chih Hung Lo, Nagamani Vunnam, Andrew K Lewis, Ting-Lan Chiu, Benjamin E Brummel, Tory M Schaaf, Benjamin D Grant, Prachi Bawaskar, David D Thomas, Jonathan N Sachs
Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that binds tumor necrosis factor or lymphotoxin-alpha and plays a critical role in regulating the inflammatory response. Upregulation of these ligands is associated with inflammatory and autoimmune diseases. Current treatments reduce symptoms by sequestering free ligands, but this can cause adverse side effects by unintentionally inhibiting ligand binding to off-target receptors. Hence, there is a need for new small molecules that specifically target the receptors, rather than the ligands...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#4
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28495792/cd70-reverse-signaling-enhances-nk-cell-function-and-immunosurveillance-in-cd27-expressing-b-cell-malignancies
#5
Mohamad F Al Sayed, Carla A Ruckstuhl, Tamara Hilmenyuk, Christina Claus, Jean-Pierre Bourquin, Beat C Bornhauser, Ramin Radpour, Carsten Riether, Adrian F Ochsenbein
The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells (Tregs). Similar to other TNFR-ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B cell non-Hodgkin lymphoma (NHL), but its role in the immune control of lymphoma and leukemia is unknown...
May 11, 2017: Blood
https://www.readbyqxmd.com/read/28495615/a-novel-function-of-tlr4-in-mediating-the-immunomodulatory-effect-of-benzanthrone-an-environmental-pollutant
#6
Prachi Tewari, Payal Mandal, Ruchi Roy, Somya Asthana, Premendra D Dwivedi, Mukul Das, Anurag Tripathi
Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated...
May 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28476763/plasma-biomarkers-and-kidney-function-decline-in-early-and-established-diabetic-kidney-disease
#7
Steven G Coca, Girish N Nadkarni, Yuan Huang, Dennis G Moledina, Veena Rao, Jane Zhang, Bart Ferket, Susan T Crowley, Linda F Fried, Chirag R Parikh
Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D)...
May 5, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28473315/4-1bb-enhanced-expansion-of-cd8-til-from-triple-negative-breast-cancer-unveils-mutation-specific-cd8-t-cells
#8
Michiko Harao, Marie-Andrée Forget, Jason Roszik, Hui Gao, Gildy V Babiera, Savitri Krishnamurthy, Jessica A Chacon, Shumin Li, Elizabeth A Mittendorf, Sarah M DeSnyder, Korrene F Rockwood, Chantale Bernatchez, Naoto T Ueno, Laszlo G Radvanyi, Luis Vence, Cara Haymaker, James M Reuben
Triple negative breast cancer (TNBC) highly infiltrated with CD8(+) tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8(+) TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8(+) TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody  (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8(+) T cells...
May 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28462525/caspase-8-regulating-life-and-death
#9
REVIEW
Bart Tummers, Douglas R Green
Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best-known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28461572/group-b-streptococci-induce-proinflammatory-responses-via-a-protein-kinase-d1-dependent-pathway
#10
Kirtikumar Upadhyay, Jeoung-Eun Park, Tae Won Yoon, Priyanka Halder, Young-In Kim, Victoria Metcalfe, Ajay J Talati, B Keith English, Ae-Kyung Yi
Group B streptococci (GBS) are one of the leading causes of life-threatening illness in neonates. Proinflammatory responses to GBS mediated through host innate immune receptors play a critical role in the disease manifestation. However, the mechanisms involved in proinflammatory responses against GBS, as well as the contribution of signaling modulators involved in host immune defense, have not been fully elucidated. In the present study, we investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446565/murinization-and-h-chain-isotype-matching-of-the-anti-gitr-antibody-dta-1-reduces-immunogenicity-mediated-anaphylaxis-in-c57bl-6-mice
#11
Nicole A Belmar, Sarah W Chan, Melvin I Fox, Josue A Samayoa, Marcia M Stickler, Ninian N Tran, Yoshiko Akamatsu, Diane Hollenbaugh, Fiona A Harding, Hamsell M Alvarez
Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28420753/the-kinase-tpl2-activates-erk-and-p38-signaling-to-promote-neutrophilic-inflammation
#12
Kate Senger, Victoria C Pham, Eugene Varfolomeev, Jason A Hackney, Cesar A Corzo, Jenna Collier, Vivian W C Lau, Zhiyu Huang, Kajal Hamidzhadeh, Patrick Caplazi, Ivan Peng, A Francesca Setiadi, Ross Francis, Andres Paler-Martinez, Youngsu C Kwon, Vladimir Ramirez-Carrozzi, Yonglian Sun, Patricia W Grigg, Merone Roose-Girma, Surinder Jeet, Kai H Barck, Anna Pham, Naruhisa Ota, Connie Ha, Jeremy Stinson, Joseph Guillory, Lucinda Tam, Zora Modrusan, Claire Emson, Brent S McKenzie, Michael J Townsend, Richard A D Carano, Søren Warming, Domagoj Vucic, Jason DeVoss, Wyne P Lee, Jennie R Lill, Ali A Zarrin
Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases MEK1 and MEK2 (MEK1/2), which, in turn, activate the MAPKs extracellular signal-regulated kinase 1 (ERK1) and ERK2 (ERK1/2) in macrophages stimulated through the interleukin-1 receptor (IL-1R), Toll-like receptors (TLRs), or the tumor necrosis factor receptor (TNFR). We describe a conserved and critical role for TPL2 in mediating the effector functions of neutrophils through the activation of the p38 MAPK signaling pathway...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#13
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28412413/activation-of-muscarinic-receptors-prevents-tnf-%C3%AE-mediated-intestinal-epithelial-barrier-disruption-through-p38-mapk
#14
Junsuke Uwada, Takashi Yazawa, Md Tariqul Islam, Md Rafiqul Islam Khan, Susanne M Krug, Michael Fromm, Shin-Ichiro Karaki, Yuichi Suzuki, Atsukazu Kuwahara, Hatsumi Yoshiki, Kiyonao Sada, Ikunobu Muramatsu, Takanobu Taniguchi
Intestinal epithelial cells form a tight barrier to act as selective physical barriers, repelling hostile substances. Tumor necrosis factor-α (TNF-α) is a well characterized pro-inflammatory cytokine which can compromise intestinal barrier function and the suppression of TNF-α function is important for treatment of inflammatory bowel disease (IBD). In this study, we investigated the contribution of G-protein-coupled receptor (GPCR)-induced signalling pathways to the maintenance of epithelial barrier function...
April 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28411279/characterization-and-interspecies-scaling-of-rhtnf-%C3%AE-pharmacokinetics-with-minimal-physiologically-based-pharmacokinetic-mpbpk-models
#15
Xi Chen, Debra C DuBois, Richard R Almon, William J Jusko
Tumor necrosis factor-α (TNF-α) is a soluble cytokine and target of specific monoclonal antibodies (mAbs) and other biological agents used for the treatment of inflammatory diseases. These biologics exert their pharmacological effects through binding and neutralizing TNF-α, and thus prevent TNF-α from interacting with its cell surface receptors. The magnitude of pharmacological effects is governed not only by the pharmacokinetics of mAbs, but also the kinetic fate of TNF-α. We have examined the pharmacokinetics of rhTNF-α in rats at low doses and quantitatively characterized its pharmacokinetic features with a minimal physiologically-based pharmacokinetic (mPBPK) model...
April 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28405520/the-immune-molecular-landscape-of-the-b7-and-tnfr-immunoregulatory-ligand-receptor-families-in-head-and-neck-cancer-a-comprehensive-overview-and-the-immunotherapeutic-implications
#16
Yu-Pei Chen, Jian Zhang, Ya-Qin Wang, Na Liu, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma
The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of the immune molecular landscapes of the B7 and TNFR families would guide head and neck immuno-oncology clinical research. We performed comprehensive molecular profiling of 10 B7 and 6 TNFR family members in head and neck cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28392436/an-oral-administration-of-a-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-promoting-regulatory-t-cells-results-of-a-phase-i-clinical-trial-using-a-novel-oral-anti-tnf-alpha-based-therapy
#17
Einat Almon, Tawfik Khoury, Ariel Drori, Svetlana Gingis-Velitski, Sari Alon, Raul Chertkoff, Mordechai Mushkat, Yoseph Shaaltiel, Yaron Ilan
BACKGROUND: An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. METHODS: Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants...
April 7, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28389814/effect-of-tonsillectomy-with-steroid-pulse-therapy-on-circulating-tumor-necrosis-factor-receptors-1-and-2-in-iga-nephropathy
#18
Maki Murakoshi, Tomohito Gohda, Yuji Sonoda, Hitoshi Suzuki, Yasuhiko Tomino, Satoshi Horikoshi, Yusuke Suzuki
BACKGROUND: High circulating levels of soluble tumor necrosis factor receptors (TNFRs: TNFR1, TNFR2) predict renal function decline in a variety of kidney diseases. Tonsillectomy with steroid pulse (TSP) therapy has been reported as a remission induction therapy in IgA nephropathy (IgAN), mainly in Japan. However, little is known about whether TNFR levels change after TSP therapy in patients with IgAN. METHODS: Two hundred twenty-three patients with IgAN were stratified according to the estimated glomerular filtration rate (eGFR): Group I (eGFR ≥ 60 mL/min/1...
April 7, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28367848/tnf-receptor-1-2-predict-heart-failure-risk-in-type-2-diabetes-mellitus-patients
#19
Zhang Ping, Ma Aiqun, Li Jiwu, Shao Liang
Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86)...
April 6, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28365939/high-expression-of-herpesvirus-entry-mediator-hvem-in-ovarian-serous-adenocarcinoma-tissue
#20
Yuan Fang, Lei Ye, Ting Zhang, Qi-Zhi He, Jian-Long Zhu
PURPOSE: To explore the expression of herpesvirus entry mediator (HVEM) in ovarian serous adenocarcinoma tissues and its relationship with clinicopathological features. METHODS: Paraffin-embedded specimens from 40 patients with ovarian serous adenocarcinoma who were subjected to surgical treatment were used for the determination of HVEM expression by immunohistochemistry (IHC). Then the relationship between the expression of HVEM and the patient clinicopathological features was analyzed...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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