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Immune programming

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https://www.readbyqxmd.com/read/29149667/tumor-acidosis-and-hypoxia-differently-modulate-the-inflammatory-program-measurements-in-vitro-and-in-vivo
#1
Anne Riemann, Sarah Reime, Oliver Thews
Inflammatory mediators produced by the tumor cells are of importance for immune response but also for malignant progression. The aim of the study was to analyze the expression of monocyte chemoattractant protein-1, interleukin-6 (IL-6), tumor necrosis factor-α, inducible isoform of nitric oxide synthase (iNOS), cyclooxygenase-2, and osteopontin in vitro in two different tumor cell lines under hypoxia (pO2≈1.5 mmHg) and/or acidosis (pH=6.6) for up to 24 hours since hypoxia and acidosis are common characteristics of solid tumors...
November 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29149303/changes-in-cytokine-filarial-antigen-and-dna-levels-associated-with-adverse-events-following-treatment-of-lymphatic-filariasis
#2
Britt J Andersen, Jessica Kumar, Kurt Curtis, Nelly Sanuku, Samson Satofan, Christopher L King, Peter U Fischer, Gary J Weil
Background: Mild to moderate adverse events (AEs) are common after treatment of lymphatic filariasis (LF) and pose a major challenge for the global LF elimination program. We studied changes in cytokine levels and filarial worm components in plasma of subjects with and without AEs following treatment of LF. Methods: Participants (N=24) were hospitalized and monitored for AEs following treatment. Cytokines (27), filarial DNA, circulating filarial antigen (CFA), and immune complexes were measured in plasma samples collected before and after treatment...
November 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29148965/nonclinical-safety-assessment-of-anti-factor-d-key-strategies-and-challenges-for-the-nonclinical-development-of-intravitreal-biologics
#3
Vladimir Bantseev, Rebecca Erickson, Douglas Leipold, Caroline Amaya, Paul E Miller, Helen Booler, Evan A Thackaberry
PURPOSE: The nonclinical toxicology program described here was designed to characterize the safety profile of anti-factor D (AFD; FCFD4514S, lampalizumab) to support intravitreal (ITV) administration in patients with geographic atrophy (GA). METHODS: The toxicity of AFD was assessed in a single-dose and 6-month repeat-dose study in monkeys at doses up to 10 mg/eye. Toxicity was assessed by clinical ophthalmic examinations, intraocular pressure measurements, ocular photography, electroretinography, fluorescein angiography, optical coherence tomography, and anatomic pathology...
November 17, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29148958/human-leptospirosis-vaccines-in-china
#4
Yinghua Xu, Qiang Ye
The present incidence of leptospirosis in China is significantly lower than past rates, although small localized outbreaks continue to occur in epidemic regions. Improvements in sanitation, as well as vaccination of high-risk populations, have played crucial roles in reducing the disease burden. Several types of human leptospirosis vaccines have been developed, including inactivated whole-cell, outer-envelope, and recombinant vaccines. Of these, only a multivalent inactivated leptospirosis vaccine is available in China, which was added to the Chinese Expanded Program on Immunization in 2007...
November 17, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29148731/conjugation-of-transforming-growth-factor-beta-to-antigen-loaded-poly-lactide-co-glycolide-nanoparticles-enhances-efficiency-of-antigen-specific-tolerance
#5
Liam M Casey, Ryan M Pearson, Kevin Hughes, Jeffrey Liu, Justin Rose, Madeleine G North, Leon Wang, Lei Mei, Stephen D Miller, Lonnie D Shea
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen(Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that co-delivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#6
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#7
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#8
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#9
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147602/gdnf-secreted-by-nerves-enhances-pd-l1-expression-via-jak2-stat1-signaling-activation-in-hnscc
#10
Chengzhong Lin, Wei Cao, Zhenhu Ren, Yu Tang, Chunye Zhang, Rong Yang, Yiming Chen, Zheqi Liu, Canbang Peng, Lizhen Wang, Xu Wang, Tong Ji
Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146737/rheumatic-disorders-associated-with-immune-checkpoint-inhibitors-in-patients-with-cancer-clinical-aspects-and-relationship-with-tumour-response-a-single-centre-prospective-cohort-study
#11
Marie Kostine, Léa Rouxel, Thomas Barnetche, Rémi Veillon, Florent Martin, Caroline Dutriaux, Léa Dousset, Anne Pham-Ledard, Sorilla Prey, Marie Beylot-Barry, Amaury Daste, Marine Gross-Goupil, Julie Lallier, Alain Ravaud, Edouard Forcade, Bernard Bannwarth, Marie-Elise Truchetet, Christophe Richez, Nadia Mehsen, Thierry Schaeverbeke
OBJECTIVES: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. METHODS: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management...
November 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#12
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146060/clinicopathologic-correlation-of-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinomas-a-report-from-india
#13
Archana George Vallonthaiel, Prabhat Singh Malik, Varsha Singh, Vinay Kumar, Sunil Kumar, Mehar Chand Sharma, Sandeep Mathur, Sudheer Arava, Randeep Guleria, Deepali Jain
INTRODUCTION: Increased expression of Programmed death ligand-1 (PD-L1) on cancer cells and immune cells predict response to PD-1/PDL1 inhibitors. Data regarding frequency and pattern of PD-L1 expression in NSCLC from India is not available. OBJECTIVES: To analyse PD-L1 expression on tumour cells (TC) and immune cells (IC) and to correlate PD-L1 expression with baseline clinico-pathological characteristics, oncogenic drivers and outcome data. MATERIALS AND METHODS: PD-L1 expression on tumour cells and immune cells was analysed...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29145871/challenges-to-implementing-gavi-s-health-system-strengthening-support-in-chad-and-cameroon-results-from-a-mixed-methods-evaluation
#14
Emily Dansereau, Yodé Miangotar, Ellen Squires, Honoré Mimche, Charbel El Bcheraoui
BACKGROUND: Since 2005, Gavi has provided health system strengthening (HSS) grants to address bottlenecks affecting immunization services. This study is the first to evaluate the Gavi HSS implementation process in either Cameroon or Chad, two countries with significant health system challenges and poor achievement on the child and maternal health Millennium Development Goals. METHODS: We triangulated quantitative and qualitative data including financial records, document review, field visit questionnaires, and key informant interviews (KII) with representatives from the Ministries of Health, Gavi, and other partners...
November 16, 2017: Globalization and Health
https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#15
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29145358/progress-in-rubella-and-congenital-rubella-syndrome-control-and-elimination-worldwide-2000-2016
#16
Gavin B Grant, Susan E Reef, Minal Patel, Jennifer K Knapp, Alya Dabbagh
Although rubella virus infection usually causes a mild fever and rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome (CRS) (1). Rubella is a leading vaccine-preventable cause of birth defects. Preventing these adverse pregnancy outcomes is the focus of rubella vaccination programs. In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national immunization schedules and recommended an initial vaccination campaign, usually targeting children aged 9 months-14 years (1)...
November 17, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29145357/global-routine-vaccination-coverage-2016
#17
Leora R Feldstein, Stephanie Mariat, Marta Gacic-Dobo, Mamadou S Diallo, Laura M Conklin, Aaron S Wallace
The Global Vaccine Action Plan 2011-2020 (GVAP) (1), endorsed by the World Health Assembly in 2012, calls on all countries to reach ≥90% national coverage for all vaccines in the country's routine immunization schedule by 2020. CDC and the World Health Organization (WHO) evaluated the WHO and United Nations Children's Fund (UNICEF) global vaccination coverage estimates to describe changes in global and regional coverage as of 2016. Global coverage estimates for the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP3), the third dose of polio vaccine, and the first dose of measles-containing vaccine (MCV1) have ranged from 84% to 86% since 2010...
November 17, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29144791/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-i-colorectal-cancer-microsatellite-instability-testing-and-clinical-implications
#18
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29144463/a-single-cell-survey-of-the-small-intestinal-epithelium
#19
Adam L Haber, Moshe Biton, Noga Rogel, Rebecca H Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M Delorey, Michael R Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J Xavier, Aviv Regev
Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144460/inflammation-induced-iga-cells-dismantle-anti-liver-cancer-immunity
#20
Shabnam Shalapour, Xue-Jia Lin, Ingmar N Bastian, John Brain, Alastair D Burt, Alexander A Aksenov, Alison F Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani, Zhenyu Zhong, Debanjan Dhar, Jose A Navas-Molina, Jun Xu, Rohit Loomba, Michael Downes, Ruth T Yu, Ronald M Evans, Pieter C Dorrestein, Rob Knight, Christopher Benner, Quentin M Anstee, Michael Karin
The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA(+)) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8(+) T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens...
November 16, 2017: Nature
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