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Programmed Cell death AND disease

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https://www.readbyqxmd.com/read/28644437/more-alive-than-dead-non-apoptotic-roles-for-caspases-in-neuronal-development-plasticity-and-disease
#1
REVIEW
Amrita Mukherjee, Darren W Williams
Nervous systems are arguably the most fascinating and complex structures in the known universe. How they are built, changed by experience and then degenerate are some of the biggest questions in biology. Regressive phenomena, such as neuron pruning and programmed cell death, have a key role in the building and maintenance of the nervous systems. Both of these cellular mechanisms deploy the caspase family of protease enzymes. In this review, we highlight the non-apoptotic function of caspases during nervous system development, plasticity and disease, particularly focussing on their role in structural remodelling...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28643244/durvalumab-first-global-approval
#2
Yahiya Y Syed
Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy...
June 22, 2017: Drugs
https://www.readbyqxmd.com/read/28638740/tumor-cells-pd-l1-expression-as-a-favorable-prognosis-factor-in-nasopharyngeal-carcinoma-patients-with-pre-existing-intratumor-infiltrating-lymphocytes
#3
Qian Zhu, Mu-Yan Cai, Chang-Long Chen, Hao Hu, Huan-Xin Lin, Min Li, De-Sheng Weng, Jing-Jing Zhao, Ling Guo, Jian-Chuan Xia
Programmed death ligand 1 (PD-L1) expression represents a mechanism of immune escape by inhibiting T cell immunity. This study systematically evaluated the expression of PD-L1, spatial distribution of CD3(+) immune cells and the relationship of both factors to survival in nasopharyngeal carcinoma (NPC) patients. A total of 209 NPC patients treated between 1991 and 2000 were included. Pairs of TMAs were immunohistochemically stained with PD-L1 and CD3. Survival analysis was evaluated according to PD-L1 status and the spatial distribution of CD3(+) immune cells in the primary lesion microenvironment...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638381/anti-bovine-programmed-death-1-rat-bovine-chimeric-antibody-for-immunotherapy-of-bovine-leukemia-virus-infection-in-cattle
#4
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Chie Nakajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#5
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28636851/first-line-nivolumab-in-stage-iv-or-recurrent-non-small-cell-lung-cancer
#6
COMMENT
David P Carbone, Martin Reck, Luis Paz-Ares, Benjamin Creelan, Leora Horn, Martin Steins, Enriqueta Felip, Michel M van den Heuvel, Tudor-Eliade Ciuleanu, Firas Badin, Neal Ready, T Jeroen N Hiltermann, Suresh Nair, Rosalyn Juergens, Solange Peters, Elisa Minenza, John M Wrangle, Delvys Rodriguez-Abreu, Hossein Borghaei, George R Blumenschein, Liza C Villaruz, Libor Havel, Jana Krejci, Jesus Corral Jaime, Han Chang, William J Geese, Prabhu Bhagavatheeswaran, Allen C Chen, Mark A Socinski
BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. METHODS: We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles)...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28635519/the-elicitor-protein-ases-induces-a-sar-response-accompanied-by-systemic-microbursts-and-micro-hrs-in-fragaria-ananassa
#7
Verónica Hael Conrad, Silvia Marisa Perato, Marta Elena Arias, Martín Gustavo Martínez Zamora, Pía de Los Ángeles Di Peto, Gustavo Gabriel Martos, Atilio Pedro Castagnaro, Juan Carlos Diaz-Ricci, Nadia Regina Chalfoun
The elicitor AsES (Acremonium strictum Elicitor Subtilisin) is a 34 KDa subtilisin-like protein secreted by the opportunistic fungus Acremonium strictum. AsES activates the innate immunity and confers resistance against anthracnose and grey mold diseases in strawberry plants (Fragaria x ananassa Duch.) and the last disease also in Arabidopsis. In the present work, we show that upon AsES recognition, a cascade of defense responses is activated, including: calcium influx, biphasic oxidative burst (O2(.-) and H2O2), HR response, accumulation of autofluorescent compounds, cell wall reinforcement with callose and lignin deposition, salicylic acid accumulation, and expression of defense-related genes such as FaPR1, FaPG1, FaMYB30, FaRBOH-D, FaRBOH-F, FaCHI23 and FaFLS...
June 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#8
Laetitia Laurent, Awena Lefur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic Lupus Erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28631096/a-case-of-nivolumab-related-cholangitis-and-literature-review-how-to-look-for-the-right-tools-for-a-correct-diagnosis-of-this-rare-immune-related-adverse-event
#9
Francesco Gelsomino, Giovanni Vitale, Andrea Ardizzoni
Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28625883/tcr-cd3-cd4-cd8-effector-t-cells-in-psoriasis
#10
D Brandt, M Sergon, S Abraham, K Mäbert, C M Hedrich
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive...
June 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28625638/development-of-psoriatic-arthritis-during-nivolumab-therapy-for-metastatic-non-small-cell-lung-cancer-clinical-outcome-analysis-and-review-of-the-literature
#11
Juan Ruiz-Bañobre, Eva Pérez-Pampín, Jorge García-González, Antonio Gómez-Caamaño, Francisco Javier Barón-Duarte, Rafael López-López, Francisca Vázquez-Rivera
Lung cancer is the leading cause of cancer-related death worldwide. The most common type, non-small cell lung cancer (NSCLC), is further divided into two main types, squamous cell and non-squamous cell (which includes adenocarcinoma). Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to docetaxel, but also a relatively good side-effect profile among patients with previously treated advanced squamous and non-squamous NSCLC...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625152/lipid-oxidation-products-in-the-pathogenesis-of-inflammation-related-gut-diseases
#12
Barbara Sottero, Daniela Rossin, Giuseppe Poli, Fiorella Biasi
A defective mucosal barrier function is the principal cause of the uncontrolled onset and progression of a number of human inflammatory gut diseases, most of which are characterized by chronic intermittent immune and inflammatory responses leading to structural intestinal damage, which can represent a potential risk for colorectal cancer development. During the active disease phase the production of pro-inflammatory cytokines and chemokines, and the induction of oxidative reactions by activated leukocytes and epithelial cells represent the main event in intestinal inflammation...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28624922/targeting-the-pd-1-pd-l1-immune-checkpoint-in-egfr-mutated-or-alk-translocated-non-small-cell-lung-cancer
#13
Olivier Bylicki, Nicolas Paleiron, Jacques Margery, Florian Guisier, Alain Vergnenegre, Gilles Robinet, Jean-Bernard Auliac, Radj Gervais, Christos Chouaid
Immune checkpoint inhibitors, notably antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28623122/a-randomized-phase-ii-study-comparing-nivolumab-with-carboplatin-pemetrexed-for-patients-with-egfr-mutation-positive-nonsquamous-non-small-cell-lung-cancer-who-acquire-resistance-to-tyrosine-kinase-inhibitors-not-due-to-a-secondary-t790m-mutation-rationale
#14
Hidetoshi Hayashi, Yasutaka Chiba, Kazuko Sakai, Tomonobu Fujita, Hiroshige Yoshioka, Daisuke Sakai, Chiyoe Kitagawa, Tateaki Naito, Koji Takeda, Isamu Okamoto, Tetsuya Mitsudomi, Yutaka Kawakami, Kazuto Nishio, Shinichiro Nakamura, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Antibodies to programmed cell death-1 (PD-1), such as nivolumab, have shown promising clinical activity in patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy appears to be less pronounced in patients with such tumors harboring epidermal growth factor receptor gene (EGFR) mutations. Recent findings suggest that patients with EGFR mutation-positive NSCLC who develop resistance to tyrosine kinase inhibitors (TKIs) due to mechanisms other than acquisition of the secondary T790M mutation of EGFR are more likely to benefit from nivolumab treatment, possibly as a result of a higher level of expression of the PD-1 ligand PD-L1, than are patients who are T790M-positive...
May 25, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28621686/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#15
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619747/successful-immune-checkpoint-blockade-in-a-patient-with-advanced-stage-microsatellite-unstable-biliary-tract-cancer
#16
Elena Czink, Matthias Kloor, Benjamin Goeppert, Stefan Froehling, Sebastian Uhrig, Tim F Weber, Joern Meinel, Christian Sutter, Karl Heinz Weiss, Peter Schirmacher, Magnus von Knebel Doeberitz, Dirk Jaeger, Christoph Springfeld
Cancers acquire multiple somatic mutations that can lead to the generation of immunogenic mutation-induced neoantigens. These neoantigens can be recognized by the host's immune system. However, continuous stimulation of immune cells against tumor antigens can lead to immune cell exhaustion, which allows uncontrolled outgrowth of tumor cells. Recently, immune checkpoint inhibitors have emerged as a novel approach to overcome immune cell exhaustion and re-activate anti-tumor immune responses. In particular, antibodies blocking the exhaustion-mediating programmed death receptor (PD-1)/PD-L1 pathway have shown clinical efficacy...
June 15, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28604812/prognostic-value-of-programmed-cell-death-ligand-1-expression-in-patients-with-head-and-neck-cancer-a-systematic-review-and-meta-analysis
#17
Ji Li, Ping Wang, Youliang Xu
BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression was reported to be correlated with poor prognosis in various cancers. However, the relationship between PD-L1 expression and the survival of patients with head and neck cancer (HNC) remains inconclusive. In the present study, we aimed to clarify the prognostic value of PD-L1 in HNC patients using meta-analysis techniques. METHODS: A comprehensive database searching was conducted in the PubMed, EMBASE, Web of Science and Cochrane Library from inception to August 2016...
2017: PloS One
https://www.readbyqxmd.com/read/28604383/pyruvate-controls-the-checkpoint-inhibitor-pd-l1-and-suppresses-t-cell-immunity
#18
Ryu Watanabe, Tsuyoshi Shirai, Hong Namkoong, Hui Zhang, Gerald J Berry, Barbara B Wallis, Benedikt Schaefgen, David G Harrison, Jennifer A Tremmel, John C Giacomini, Jörg J Goronzy, Cornelia M Weyand
Patients with coronary artery disease (CAD) are at high risk for reactivation of the varicella zoster virus (VZV) and development of herpes zoster (HZ). Here, we found that macrophages from patients with CAD actively suppress T cell activation and expansion, leading to defective VZV-specific T cell immunity. Monocyte-derived and plaque-infiltrating macrophages from patients with CAD spontaneously expressed high surface density of the immunoinhibitory ligand programmed death ligand-1 (PD-L1), thereby providing negative signals to programmed death-1+ (PD-1+) T cells...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28600350/rheumatoid-arthritis-and-polymyalgia-rheumatica-occurring-after-immune-checkpoint-inhibitor-treatment
#19
Rakiba Belkhir, Sébastien Le Burel, Laetitia Dunogeant, Aurélien Marabelle, Antoine Hollebecque, Benjamin Besse, Alexandra Leary, Anne-Laure Voisin, Clémence Pontoizeau, Laetitia Coutte, Edouard Pertuiset, Gaël Mouterde, Olivier Fain, Olivier Lambotte, Xavier Mariette
OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. METHODS: This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR...
June 9, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28592763/malignant-lymphoma-pathophysiology-and-current-therapy
#20
Koji Izutsu
Recent advances in the understanding of molecular pathogenesis of lymphoma have enabled us to clearly define disease entity by means of a disease-specific gene mutation and to select candidates for novel targeted therapy. In this review three different clinically relevant topics related to the molecular pathogenesis of lymphoma were covered. In the 2016 revision of the World Health Organization classification of lymphoid malignancies, firstly, disease-specific mutations such as MYD88 L265P in Waldenström macroglobulinemia and BRAF V600E in hairy cell leukemia were incorporated into diagnostic tests, and secondly, the determination of cell-of-origin in diffuse large B-cell lymphoma (DLBCL) was strongly recommended in diagnosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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