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Immune programming

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https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#1
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#2
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212990/high-plasma-levels-of-soluble-programmed-cell-death-ligand-1-are-prognostic-for-reduced-survival-in-advanced-lung-cancer
#3
Yusuke Okuma, Yukio Hosomi, Yoshiro Nakahara, Kageaki Watanabe, Yukiko Sagawa, Sadamu Homma
OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212734/role-of-granule-proteases-in-the-life-and-death-of-neutrophils
#4
REVIEW
Charaf Benarafa, Hans-Uwe Simon
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212523/redox-regulation-in-metabolic-programming-and-inflammation
#5
REVIEW
Helen R Griffiths, Dan Gao, Chathyan Pararasa
Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#6
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28212290/defining-clinical-response-criteria-and-early-response-criteria-for-precision-oncology-current-state-of-the-art-and-future-perspectives
#7
Vivek Subbiah, Hubert H Chuang, Dhiraj Gambhire, Kalevi Kairemo
In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016...
February 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/28212060/pembrolizumab-as-second-line-therapy-for-advanced-urothelial-carcinoma
#8
Joaquim Bellmunt, Ronald de Wit, David J Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Yabing Mai, Christian H Poehlein, Rodolfo F Perini, Dean F Bajorin
Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine...
February 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28211077/severe-bullous-pemphigoid-associated-with-pembrolizumab-therapy-for-metastatic-melanoma-with-complete-regression
#9
O Rofe, G Bar-Sela, Z Keidar, T Sezin, C D Sadik, R Bergman
Bullous pemphigoid (BP) is considered to be a humorally mediated autoimmune disease, but autoreactive T-cells and T-regulatory cells (Tregs) have also been implicated in this disease. Tregs and the programmed death-1 (PD-1) : programmed death ligand (PD-L) pathway are both critical in terminating immune response, and elimination of either can result in breakdown of tolerance and development of autoimmunity. We report a patient with metastatic malignant melanoma (MM), who underwent pembrolizumab (anti-PD-1) therapy following unsuccessful treatment with ipilimumab [anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4]...
February 16, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28210459/microbiological-qualification-of-air-water-and-dialysate-in-a-haemodialysis-centre-a-new-focus-on-legionella-spp
#10
Saeid Nazemi, Mehdi Mirzaii, Somayeh Yaslianifard, Davood Darban-Sarokhalil, Seyyed Sajjad Khoramrooz, Pirasteh Norozi, Fatemeh Davardoost
BACKGROUND AND OBJECTIVES: The microbiological monitoring of the water used for haemodialysis is important especially for Legionella and non-fermentative bacteria since patients with end stage renal disease (ESRD) are suffering from deteriorated function of immune system. MATERIALS AND METHODS: A total 50 water and dialysate samples were weekly collected over a period of 10 weeks from 5 sites. Total and faecal coliforms were determined by utilizing the most probable number (MPN) method...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209436/is-colombia-reaching-the-goals-on-infant-immunization-coverage-a-quantitative-survey-from-80-municipalities
#11
Javier Narváez, May Bibiana Osorio, Carlos Castañeda-Orjuela, Nelson Alvis Zakzuk, Natalia Cediel, Luz Ángela Chocontá-Piraquive, Fernando de La Hoz-Restrepo
OBJECTIVES: This study aimed to evaluate the coverage of the Colombian Expanded Program on Immunization among children less than 6years old, to evaluate the timeliness of immunization, to assess the coverage of newly introduced vaccines, and to identify factors associated with lack of immunization. METHODS: We conducted a cross-sectional survey in 80 municipalities of Colombia, using a two-stage cluster random sampling. We attempted to contact all children less than 6years old living in the sampled blocks, and asked their caregivers to provide immunization record cards...
February 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28208120/cardiovascular-complications-of-hiv-infection
#12
Marshall J Glesby
HIV-infected individuals are at increased risk for cardiovascular events. Widely used cardiovascular disease (CVD) risk calculators to determine indications for statin treatment are not well validated for use in the HIV-infecte population. Some experts advocate including HIV infection as an independent risk factor for CVD. The effects of antiretroviral therapy on lipid profiles and the potentially increased risk for cardiovascular events must be taken into account when selecting treatment for HIV-infected individuals...
December 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28207888/effect-of-the-different-13-valent-pneumococcal-conjugate-vaccination-uptakes-on-the-invasive-pneumococcal-disease-in-children-analysis-of-a-hospital-based-and-population-based-surveillance-study-in-madrid-spain-2007-2015
#13
Juan Picazo, Jesús Ruiz-Contreras, Juan Casado-Flores, Sagrario Negreira, Fernando Baquero, Teresa Hernández-Sampelayo, Enrique Otheo, Cristina Méndez
In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding...
2017: PloS One
https://www.readbyqxmd.com/read/28207525/plasma-levels-of-soluble-programmed-death-ligand-1-may-be-associated-with-overall-survival-in-nonsmall-cell-lung-cancer-patients-receiving-thoracic-radiotherapy
#14
Jing Zhao, Peng Zhang, Jianhua Wang, Qingsong Xi, Xueqi Zhao, Minghua Ji, Guangyuan Hu
Immune-checkpoint signaling plays an important role in immunosuppression of tumors. We aimed to investigate the association of soluble programmed death-ligand 1 (sPD-L1) level in plasma with overall survival (OS) in locally advanced or inoperable nonsmall-cell lung cancer (NSCLC) patients treated with thoracic radiotherapy (TRT). We used ELISA to evaluate the sPD-L1 levels at diagnosis and during TRT in 126 clinically inoperable NSCLC patients. OS rates were followed up and recorded. SPSS software and GraphPad Prism 5 were used for statistics...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207501/pd-l1-pd-1-check-point-in-gastric-carcinoma-with-lymphoid-stroma-case-report-with-immunochemical-study
#15
Anna Crescenzi, Chiara Taffon, Michele Donati, Michele Pier Luca Guarino, Sergio Valeri, Roberto Coppola
INTRODUCTION: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. PATIENT'S CONCERNS CASE STUDY AND OUTCOME: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207204/concise-review-increasing-the-validity-of-cerebrovascular-disease-models-and-experimental-methods-for-translational-stem-cell-research
#16
Johannes Boltze, Franziska Nitzsche, Jukka Jolkkonen, Gesa Weise, Claudia Pösel, Björn Nitzsche, Daniel-Christoph Wagner
Interspecies differences, anatomical and physiological aspects as wells as simplified study designs contribute to an overestimation of treatment effects and limit the transferability of experimental results into clinical applications. Confounders of cell therapies for cerebrovascular disorders (CVD) include common CVD comorbidities, frequent medications potentially affecting endogenous and transplanted stem cells, as well as age- and immune-system-related effects. All of those can contribute to a substantial modelling bias, ultimately limiting the prospective quality of preclinical research programs regarding the clinical value of a particular cell therapy...
February 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28204866/vedolizumab-treatment-for-immune-checkpoint-inhibitor-induced-enterocolitis
#17
Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal
Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy...
February 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28203344/emerging-role-of-checkpoint-blockade-therapy-in-lymphoma
#18
REVIEW
Natalie Galanina, Justin Kline, Michael R Bishop
Following the successful application of immune checkpoint blockade therapy (CBT) in refractory solid tumors, it has recently gained momentum as a promising modality in the treatment of relapsed lymphoma. This significant therapeutic advance stems from decades of research that elucidated the role of immune regulation pathways and the mechanisms by which tumors can engage these critical pathways to escape immune detection. To date, two main pathways, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have emerged as key targets of CBT demonstrating unprecedented activity particularly in heavily pretreated relapsed/refractory Hodgkin lymphoma and some forms of non-Hodgkin disease...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28202921/a-human-programmed-death-ligand-1-expressing-mouse-tumor-model-for-evaluating-the-therapeutic-efficacy-of-anti-human-pd-l1-antibodies
#19
Anfei Huang, Di Peng, Huanhuan Guo, Yinyin Ben, Xiangyang Zuo, Fei Wu, Xiaoli Yang, Fei Teng, Zhen Li, Xueming Qian, F Xiao-Feng Qin
Huge efforts have been devoted to develop therapeutic monoclonal antibodies targeting human Programmed death-ligand 1 (hPD-L1) for treating various types of human cancers. However, thus far there is no suitable animal model for evaluating the anti-tumor efficacy of such antibodies against hPD-L1. Here we report the generation of a robust and effective system utilizing hPD-L1-expressing mouse tumor cells to study the therapeutic activity and mode of action of anti-human PD-L1 in mice. The model has been validated by using a clinically proven hPD-L1 blocking antibody...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#20
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
February 9, 2017: Oncotarget
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