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https://www.readbyqxmd.com/read/29772559/gitr-domain-inside-car-co-stimulates-activity-of-car-t-cells-against-cancer
#1
Vita M Golubovskaya, Robert Berahovich, Qumiao Xu, Hua Zhou, Shirley Xu, Jasper Guan, Hizkia Harto, Le Li, Lijun Wu
T cells expressing Chimeric antigen receptors or CAR-T cells are used as a novel treatment against hematological and solid cancers. In this report, we designed CAR with glucocorticoid-induced TNFR-related protein (GITR) co-stimulatory domain to study its ability to co-activate CAR-T cells. EGFR-GITR-CD3 CAR-T cells were cytotoxic against EGFR-positive: pancreatic and ovarian cancer cells but not against EGFR-negative cancer cells. The cytotoxic activity of EGFR-GITR-CD3 CAR-T cells was comparable or better than EGFR-28-CD3 or EGFR-41BB-CD3 CAR-T cells...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29769272/original-ligand-for-lt%C3%AE-r-is-light-insight-into-evolution-of-the-lt-lt%C3%AE-r-system
#2
Tomoki Maeda, Hiroaki Suetake, Tomoyuki Odaka, Toshiaki Miyadai
The lymphotoxin (LT)/LTβ receptor (LTβR) axis is crucial for the regulation of immune responses and development of lymphoid tissues in mammals. Despite the importance of this pathway, the existence and function of LT and LTβR remain obscure for nonmammalian species. In this study, we report a nonmammalian LTβR and its ligand. We demonstrate that TNF-New (TNFN), which has been considered orthologous to mammalian LT, was expressed on the cell surface as a homomer in vitro. This different protein structure indicates that TNFN is not orthologous to mammalian LTα and LTβ...
May 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#3
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29752064/cell-specific-imd-nf-%C3%AE%C2%BAb-responses-enable-simultaneous-antibacterial-immunity-and-intestinal-epithelial-cell-shedding-upon-bacterial-infection
#4
Zongzhao Zhai, Jean-Philippe Boquete, Bruno Lemaitre
Intestinal infection triggers potent immune responses to combat pathogens and concomitantly drives epithelial renewal to maintain barrier integrity. Current models propose that epithelial renewal is primarily driven by damage caused by reactive oxygen species (ROS). Here we found that in Drosophila, the Imd-NF-κB pathway controlled enterocyte (EC) shedding upon infection, via a mechanism independent of ROS-associated apoptosis. Mechanistically, the Imd pathway synergized with JNK signaling to induce epithelial cell shedding specifically in the context of bacterial infection, requiring also the reduced expression of the transcription factor GATAe...
May 3, 2018: Immunity
https://www.readbyqxmd.com/read/29748372/traf1-is-critical-for-regulating-the-braf-mek-erk-pathway-in-non-small-cell-lung-carcinogenesis
#5
Qiushi Wang, Ge Gao, Tianshun Zhang, Ke Yao, Hanyong Chen, Mi Hee Park, Hiroyuki Yamamoto, Keke Wang, Weiya Ma, Margarita Malakhova, Ann M Bode, Zigang Dong
Tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) is a unique TRAF protein that can interact directly or indirectly with multiple TNFR family members, regulatory proteins, kinases, and adaptors that contribute to its diverse functions in specific tissues. However, the role of TRAF1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we report that TRAF1 is overexpressed in human lung cancer cells and tissues. TRAF1 expression level inversely correlated with patient survival probability...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29729375/clinical-predictive-biomarkers-for-normoalbuminuric-diabetic-kidney-disease
#6
Tomohito Gohda, Yuji Nishizaki, Maki Murakoshi, Shuko Nojiri, Naotake Yanagisawa, Terumi Shibata, Mami Yamashita, Kanako Tanaka, Yoshinori Yamashita, Yusuke Suzuki, Nozomu Kamei
AIMS: A portion of patients with diabetes mellitus follow the progression of a non-albuminuria-based pathway; i.e., normoalbuminuric diabetic kidney disease (NA-DKD). However, the risk factors which determine NA-DKD are not yet fully understood. This cross-sectional study was therefore aimed to investigate the association between various biomarker levels and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus and normoalbuminuria (T2D-NA). METHODS: We measured cardiovascular disease (CVD) [serum osteoprotegerin (OPG), plasma brain natriuretic peptide (BNP), cardio-ankle vascular index (CAVI)], tubular damage [urinary L-type fatty acid binding protein (L-FABP)], and inflammatory [serum tumornecrosis factor (TNF) α and its receptors (TNFRs)] biomarkers in 314 patients with T2D-NA...
May 3, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29720399/crystal-structure-of-the-human-4-1bb-4-1bbl-complex
#7
Ryan N Gilbreth, Vaheh Y Oganesyan, Hamza Amdouni, Shabazz Novarra, Luba Grinberg, Arnita Barnes, Manuel Baca
4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29720398/crystal-structures-of-the-human-4-1bb-receptor-bound-to-its-ligand-4-1bbl-reveal-covalent-receptor-dimerization-as-a-potential-signaling-amplifier
#8
Aruna Bitra, Tzanko Doukov, Michael Croft, Dirk M Zajonc
Human (h)4-1BB (TNFRSF9 or CD137) is an inducible tumor necrosis factor receptor (TNFR) super family member that interacts with its cognate ligand h4-1BBL to promote T lymphocyte activation and proliferation. h4-1BB is currently being targeted with agonists in cancer immunotherapy. Here, we determined the crystal structures of unbound h4-1BBL and both wildtype h4-1BB and a dimerization-deficient h-41BB mutant (C121S) in complex with h4-1BBL at resolutions between 2.7 Å and 3.2 Å. We observed that the structural arrangement of 4-1BBL, both unbound and in the complex, represents the canonical bell shape as seen in other similar TNF proteins and differs from the previously reported three-bladed propeller structure of 4-1BBL...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29717111/low-doses-of-lps-exacerbate-the-inflammatory-response-and-trigger-death-on-tlr3-primed-human-monocytes
#9
Marta Monguió-Tortajada, Marcella Franquesa, Maria-Rosa Sarrias, Francesc E Borràs
TLR sensing of pathogens triggers monocyte activation to initiate the host innate immune response to infection. Monocytes can dynamically adapt to different TLR agonists inducing different patterns of inflammatory response, and the sequence of exposure to TLRs can dramatically modulate cell activation. Understanding the interactions between TLR signalling that lead to synergy, priming and tolerance to TLR agonists may help explain how prior infections and inflammatory conditioning can regulate the innate immune response to subsequent infections...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#10
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29670621/integrated-analysis-reveals-that-mir-193b-mir-671-and-trem-1-correlate-with-a-good-response-to-treatment-of-human-localized-cutaneous-leishmaniasis-caused-by-leishmania-braziliensis
#11
Sara Nunes, Icaro Bonyek Silva, Mariana Rosa Ampuero, Almério Libório Lopes de Noronha, Lígia Correia Lima de Souza, Thaizza Cavalcante Correia, Ricardo Khouri, Viviane Sampaio Boaventura, Aldina Barral, Pablo Ivan Pereira Ramos, Cláudia Brodskyn, Pablo Rafael Silveira Oliveira, Natalia Machado Tavares
Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by ex vivo validation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29648839/a-novel-immunoliposome-technology-for-enhancing-the-activity-of-agonistic-antibody-against-tumor-necrosis-factor-receptor-superfamily
#12
Takako Niwa, Yuji Kasuya, Yukie Suzuki, Kimihisa Ichikawa, Hiroko Yoshida, Akiko Kurimoto, Kento Tanaka, Koji Morita
We have developed a technology for efficiently enhancing the anti-cancer apoptosis-inducing activity of agonistic antibodies against the tumor necrosis factor receptor (TNFR) superfamily by the formation of immunoliposomes. To induce apoptosis in cancer cells, agonistic antibodies to the TNFR superfamily normally need cross-linking by internal immune effector cells via the Fc region after binding to receptors on the cell membrane. To develop apoptosis-inducing antibodies that do not require the support of cross-linking by immune cells, we prepared immunoliposomes conjugated with TRA-8, an agonistic antibody against death receptor 5 (DR5), with various densities of antibody on the liposome surface, and evaluated their activities...
April 12, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29623077/influenza-activated-ilc1s-contribute-to-antiviral-immunity-partially-influenced-by-differential-gitr-expression
#13
Neha Vashist, Stephanie Trittel, Thomas Ebensen, Benedict J Chambers, Carlos A Guzmán, Peggy Riese
Innate lymphoid cells (ILCs) represent diversified subsets of effector cells as well as immune regulators of mucosal immunity and are classified into group 1 ILCs, group 2 ILCs, and group 3 ILCs. Group 1 ILCs encompass natural killer (NK) cells and non-NK ILCs (ILC1s) and mediate their functionality via the rapid production of IFN-γ and TNF-α. The current knowledge of ILC1s mainly associates them to inflammatory processes. Much less is known about their regulation during infection and their capacity to interact with cells of the adaptive immune system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29619032/an-autocrine-tnf%C3%AE-tumor-necrosis-factor-receptor-2-loop-promotes-epigenetic-effects-inducing-human-treg-stability-in-vitro
#14
Paulo C M Urbano, Hans J P M Koenen, Irma Joosten, Xuehui He
A crucial issue for Treg-based immunotherapy is to maintain a bona fide Treg phenotype as well as suppressive function during and after ex vivo expansion. Several strategies have been applied to harness Treg lineage stability. For instance, CD28 superagonist stimulation in vitro , in the absence of CD3 ligation, is more efficient in promoting Treg proliferation, and prevention of pro-inflammatory cytokine expression, such as IL-17, as compared to CD3/CD28-stimulated Treg. Addition of the mTOR inhibitor rapamycin to Treg cultures enhances FOXP3 expression and Treg stability, but does impair proliferative capacity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29579081/genetics-in-tnf-tnfr-pathway-a-complex-network-causing-spondyloarthritis-and-conditioning-response-to-anti-tnf%C3%AE-therapy
#15
Ada Aita, Daniela Basso, Roberta Ramonda, Stefania Moz, Mariagrazia Lorenzin, Filippo Navaglia, Carlo-Federico Zambon, Andrea Padoan, Mario Plebani, Leonardo Punzi
OBJECTIVES: We investigated whether polymorphisms (SNPs) in the promoter region of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27 in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNFα treatment. METHODS: 373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNFα inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed by RT-PCR...
2018: PloS One
https://www.readbyqxmd.com/read/29575262/structural-basis-for-tumor-necrosis-factor-blockade-with-the-therapeutic-antibody-golimumab
#16
Masatsugu Ono, Shoichiro Horita, Yumi Sato, Yayoi Nomura, So Iwata, Norimichi Nomura
Tumor necrosis factor α (TNFα) is a proinflammatory cytokine, and elevated levels of TNFα in serum are associated with various autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and systemic lupus erythaematosus. TNFα performs its pleiotropic functions by binding to two structurally distinct transmembrane receptors, TNF receptor (TNFR) 1 and TNFR2. Antibody-based therapeutic strategies that block excessive TNFα signaling have been shown to be effective in suppressing such harmful inflammatory conditions...
March 25, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29545797/death-receptor-3-signaling-controls-the-balance-between-regulatory-and-effector-lymphocytes-in-samp1-yitfc-mice-with-crohn-s-disease-like-ileitis
#17
Zhaodong Li, Ludovica F Buttó, Kristine-Anne Buela, Li-Guo Jia, Minh Lam, John D Ward, Theresa T Pizarro, Fabio Cominelli
Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH 1), type-2 (TH 2), and type-17 (TH 17) responses as well as regulatory T cell (Treg ) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29545793/src-family-kinases-regulate-interferon-regulatory-factor-1-k63-ubiquitination-following-activation-by-tlr7-8-vaccine-adjuvant-in-human-monocytes-and-b-cells
#18
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29506619/enhanced-expression-of-tnf-%C3%AE-type-1-receptors-by-immune-cells-in-active-pulmonary-tuberculosis
#19
A A Alshevskaya, F D Kireev, Z A Laushkina, J A Lopatnikova, V S Gladkikh, J A Sennikova, A V Karaulov, S V Sennikov
BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE: To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29458298/%C3%AE-amyloid-inhibits-hippocampal-ltp-through-tnfr-ikk-nf-%C3%AE%C2%BAb-pathway
#20
Manikandan Samidurai, Vijay S Ramasamy, Jihoon Jo
Objective The suppressive action of the acute application of oligomeric amyloid-β (Aβ) on hippocampal long-term potentiation (LTP) has been reported widely. Many mechanisms have been proposed for Aβ inhibited LTP induction. The inflammatory cytokine tumor necrosis factor-α (TNF-α) has also been reported to play a key role in this LTP inhibition through Aβ. However, the underlying molecular mechanisms are largely unknown. This study aimed to investigate the link between Aβ- and TNF-α-mediated hippocampal LTP inhibition...
April 2018: Neurological Research
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