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https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#1
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29656417/mirna-regulation-of-innate-immunity
#2
REVIEW
Fatemeh Momen-Heravi, Shashi Bala
MicroRNAs (miRNAs) are small noncoding RNA and are pivotal posttranscriptional regulators of both innate and adaptive immunity. They act by regulating the expression of multiple immune genes, thus, are the important elements to the complex immune regulatory network. Deregulated expression of specific miRNAs can lead to potential autoimmunity, immune tolerance, hyper-inflammatory phenotype, and cancer initiation and progression. In this review, we discuss the contributory pathways and mechanisms by which several miRNAs influence the development of innate immunity and fine-tune immune response...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29655584/nanoemulsion-adjuvant-driven-redirection-of-t-h-2-immunity-inhibits-allergic-reactions-in-murine-models-of-peanut-allergy
#3
Jessica J O'Konek, Jeffrey J Landers, Katarzyna W Janczak, Rishi R Goel, Anna M Mondrusov, Pamela T Wong, James R Baker
BACKGROUND: Immunotherapy for food allergies involves progressive increased exposures to food that result in desensitization to food allergens in some subjects but not tolerance to the food. Therefore new approaches to suppress allergic immunity to food are necessary. Previously, we demonstrated that intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal antibody and TH 17-polarized immunity, as well as systemic TH 1-biased cellular immunity with suppression of pre-existing TH 2-biased immunity...
April 11, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29655565/the-tolerogenic-role-of-ifn-%C3%AE
#4
REVIEW
Primož Rožman, Urban Švajger
Due to its extremely pleiotropic nature, the complex effects of IFN-γ exerted both on immune and non-immune cell types still remain only partially understood. The longstanding view of IFN-γ as being a predominantly inflammatory cytokine is constantly challenged by increasing demonstrations of its direct or indirect regulatory roles. Interferon-γ can exert tolerogenic effects on both innate and adaptive immune cell types, promoting tolerance of various antigen-presenting cells, and augmenting function and differentiation of regulatory T cells, respectively...
April 7, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29652676/immune-tolerance-induction-rescue-with-turoctocog-alfa-in-a-poor-risk-haemophilia-a-inhibitor-young-child-the-history-of-a-success
#5
Ezio Zanon, Marta Milan, Samantha Pasca
: The development of alloantibodies against the replacement of Factor VIII (FVIII) is the major complication in haemophilia A treatment. The gold standard to eradicate inhibitors is the immune tolerance induction (ITI), but in some cases it fails requiring another immune tolerance, defined ITI rescue (ITI-R), using a different concentrate, even though it is still debated. We report a successful case of a poor risk (titre of inhibitor at start of ITI > 10 BU/ml, peak titre on ITI > 200 BU/ml, >2 years since the inhibitor diagnosis) haemophilia A child treated with a high-dose regimen (200 UI/kg/day) turoctocog-alfa after a failed first-line ITI with octocog-alfa lasting 29 months...
April 12, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29651292/autoantibodies-to-chemokines-and-cytokines-participate-in-the-regulation-of-cancer-and-autoimmunity
#6
REVIEW
Nathan Karin
We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29650988/the-c-terminal-hret-sequence-of-kv1-3-regulates-gating-rather-than-targeting-of-kv1-3-to-the-plasma-membrane
#7
Orsolya Voros, Orsolya Szilagyi, András Balajthy, Sándor Somodi, Gyorgy Panyi, Péter Hajdu
Kv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650017/toll-like-receptors-in-lupus-nephritis
#8
REVIEW
Satish Kumar Devarapu, Hans-Joachim Anders
The pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) is based on the loss of self-tolerance against ubiquitous autoantigens involving all mechanisms of adaptive immunity. However, data accumulating over the last decade imply an important role also for numerous elements of innate immunity, namely the Toll-like receptors in the pathogenesis of SLE. Here we discuss their role in the most common organ complication of SLE, i.e. lupus nephritis. We summarize experimental and clinical data on the expression and functional contribution of the Toll-like receptors in immune complex glomerulonephritis, and intrarenal inflammation...
April 12, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29649584/molecular-cloning-expression-and-biochemical-characterization-of-hemoglobin-gene-from-ark-shell-scapharca-broughtonii
#9
Qing Zhao, Biao Wu, Zhihong Liu, Xiujun Sun, Liqing Zhou, Aiguo Yang, Gaowei Zhang
Hemoglobin, the main component of haemolymph, is widely distributed in animals. Although its important oxygen transport functions has been extensively reported, studies on the immune function of hemoglobin in mollusc are few. Research on immune of hemoglobin of ark shell Scapharca broughtonii attracted more and more attention due to its ownership of erythrocyte comparing with many other shellfish. In this study, the hemoglobin cDNA of S. broughtonii was cloned by EST and RACE methods (named as SbHb). Sequence analysis revealed that the cDNA was 946 bp in length, including an open reading frame (ORF) of 459 bp which encoded a polypeptide of 152 amino acid residues, and a 5'-untranslated region (UTR) of 313 bp, a 3'-UTR of 174 bp...
April 9, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29649469/phosphatidylserine-is-not-just-a-cleanup-crew-but-also-a-well-meaning-teacher
#10
Fiona Y Glassman, Jennifer L Schneider, Radha Ramakrishnan, Robert K Dingman, Murali Ramanathan, Richard B Bankert, Sathy V Balu-Iyer
Phosphatidylserine (PS) exposure during apoptosis leads to silent clearance of cells without adverse immune reactions to self-proteins. Given the biological functions of PS in cellular cleanup and global immunosuppression, we hypothesized that administration of PS-protein complexes would reduce immunogenicity. Here, we report that exposing Pompe disease mice to acid alpha glucosidase (rhGAA) with PS or immunosuppressant dexamethasone (Dex) resulted in lower anti-rhGAA-antibodies than in animals receiving rhGAA alone...
April 9, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29649100/targeting-the-adenosinergic-axis-in-chronic-lymphocytic-leukemia-a-way-to-disrupt-the-tumor-niche
#11
REVIEW
Tiziana Vaisitti, Francesca Arruga, Silvia Deaglio
Targeting adenosine triphosphate (ATP) metabolism and adenosinergic signaling in cancer is gaining momentum, as increasing evidence is showing their relevance in tumor immunology and biology. Chronic lymphocytic leukemia (CLL) results from the expansion of a population of mature B cells that progressively occupies the bone marrow (BM), the blood, and peripheral lymphoid organs. Notwithstanding significant progress in the treatment of these patients, the cure remains an unmet clinical need, suggesting that novel drugs or drug combinations are needed...
April 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29644994/autoimmune-hepatitis
#12
REVIEW
Giorgina Mieli-Vergani, Diego Vergani, Albert J Czaja, Michael P Manns, Edward L Krawitt, John M Vierling, Ansgar W Lohse, Aldo J Montano-Loza
Autoimmune hepatitis (AIH) is a severe liver disease that affects children and adults worldwide. The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology. AIH arises in genetically predisposed individuals when a trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune response directed against liver autoantigens; this immune response is permitted by inadequate regulatory immune control leading to a loss of tolerance...
April 12, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29644868/crispr-cas9-inhibits-multiple-steps-of-hiv-1-infection
#13
Lijuan Yin, Siqi Hu, Shan Mei, Hong Sun, Fengwen Xu, Jian Li, Weijun Zhu, Xiaoman Liu, Fei Zhao, Di Zhang, Shan Cen, Chen Liang, Fei Guo
CRISPR/Cas9 is an adaptive immune system that bacteria and archaea have evolved to resist the invading viruses and plasmid DNA by creating site-specific double-strand breaks in DNA. In this study, we have tested this gene editing system in inhibiting HIV-1 infection by targeting the viral long terminal repeat and the gene coding sequences. We observed strong inhibition of HIV-1 infection by Cas9/gRNA, which resulted not only from insertions and deletions (indels) that were introduced into viral DNA due to Cas9 cleavage, but also from the marked decrease in the levels of the late viral DNA products and the integrated viral DNA...
April 12, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29644653/specific-blockade-cd73-alters-the-exhausted-phenotype-of-t-cells-in-head-and-neck-squamous-cell-carcinoma
#14
Wei-Wei Deng, Yi-Cun Li, Si-Rui Ma, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
The adenosine-induced immunosuppression hampers the immune response toward tumor cells and facilitates the tumor cells to evade immunosurveillance. CD73, an ecto-5-nucleotidase, is the ectoenzyme dephosphorylating extracellular AMP to adenosine. Here, using immunocompetent transgenic head and neck squamous cell carcinoma (HNSCC) mouse model, immune profiling showed high expression of CD73 on CD4+ and CD8+ T cells was associated with an 'exhausted' phenotype. Further, treatment with anti-CD73 monoclonal antibody (mAb) significantly blunted the tumor growth in the mouse model, and the blockade of CD73 reversed the 'exhausted' phenotype of CD4+ and CD8+ T cells through downregulation of total expression of PD-1 and CTLA-4 on T cells...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29644505/cardiotoxicity-of-immunotherapy-incidence-diagnosis-and-management
#15
REVIEW
Aarti Asnani
PURPOSE OF REVIEW: This review describes cardiotoxicity associated with adoptive T cell therapy and immune checkpoint blockade. RECENT FINDINGS: Cardiotoxicity is a rare but potentially fatal complication associated with novel immunotherapies. Both affinity-enhanced and chimeric antigen receptor T cells have been reported to cause hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Immune checkpoint inhibitors are generally well-tolerated but have the potential to cause myocarditis, with clinical presentations ranging from asymptomatic cardiac biomarker elevation to heart failure, arrhythmia, and cardiogenic shock...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29643992/description-of-organ-specific-phenotype-and-functional-characteristics-of-tissue-resident-lymphocytes-from-liver-transplantation-donor-and-research-on-immune-tolerance-mechanism-of-liver
#16
Yunpeng Shi, Ping Zhang, Guangyi Wang, Xingkai Liu, Xiaodong Sun, Xin Zhang, Haijun Li, Jun Qi, Lei Ding, Ting Li, Ruoyan Zhang, Yuguo Chen, Jianpeng Zhou, Guoyue Lv, Zhengkun Tu
Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver. Methods: Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643856/the-contribution-of-non-professional-antigen-presenting-cells-to-immunity-and-tolerance-in-the-liver
#17
REVIEW
Christina Mehrfeld, Steven Zenner, Miroslaw Kornek, Veronika Lukacs-Kornek
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29643761/capacity-fidelity-and-noise-tolerance-of-associative-spatial-temporal-memories-based-on-memristive-neuromorphic-networks
#18
Dmitri Gavrilov, Dmitri Strukov, Konstantin K Likharev
We have calculated key characteristics of associative (content-addressable) spatial-temporal memories based on neuromorphic networks with restricted connectivity-"CrossNets." Such networks may be naturally implemented in nanoelectronic hardware using hybrid memristive circuits, which may feature extremely high energy efficiency, approaching that of biological cortical circuits, at much higher operation speed. Our numerical simulations, in some cases confirmed by analytical calculations, show that the characteristics depend substantially on the method of information recording into the memory...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29643512/innate-immune-memory-in-the-brain-shapes-neurological-disease-hallmarks
#19
Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, Thomas Ulas, Gaurav Jain, Jessica Wagner, Lisa M Häsler, Katleen Wild, Angelos Skodras, Thomas Blank, Ori Staszewski, Moumita Datta, Tonatiuh Pena Centeno, Vincenzo Capece, Md Rezaul Islam, Cemil Kerimoglu, Matthias Staufenbiel, Joachim L Schultze, Marc Beyer, Marco Prinz, Mathias Jucker, André Fischer, Jonas J Neher
Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29643440/bacterial-pore-forming-toxins-promote-the-activation-of-caspases-in-parallel-to-necroptosis-to-enhance-alarmin-release-and-inflammation-during-pneumonia
#20
Norberto Gonzalez-Juarbe, Kelley M Bradley, Ashleigh N Riegler, Luis F Reyes, Terry Brissac, Sang-Sang Park, Marcos I Restrepo, Carlos J Orihuela
Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining...
April 11, 2018: Scientific Reports
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