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https://www.readbyqxmd.com/read/29159802/adenovirus-vector-based-prime-boost-vaccination-via-heterologous-routes-induces-cervicovaginal-cd8-t-cell-responses-against-hpv16-oncoproteins
#1
Nicolas Çuburu, Selina Khan, Cynthia D Thompson, Rina Kim, Jort Vellinga, Roland Zahn, Douglas R Lowy, Gert Scheper, John T Schiller
Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPV) are the primary etiologic agents of cervical cancer and progression from persistent HPV-infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29158791/correlation-of-cancer-stem-cell-markers-and-immune-cell-markers-in-resected-non-small-cell-lung-cancer
#2
Zhaoqin Huang, Haining Yu, Jianbo Zhang, Haiyan Jing, Wanqi Zhu, Xiaolin Li, Lingling Kong, Ligang Xing, Jinming Yu, Xiangjiao Meng
Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC. Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158474/unc93b1-interacts-with-the-calcium-sensor-stim1-for-efficient-antigen-cross-presentation-in-dendritic-cells
#3
Sophia Maschalidi, Paula Nunes-Hasler, Clarissa R Nascimento, Ignacio Sallent, Valérie Lannoy, Meriem Garfa-Traore, Nicolas Cagnard, Fernando E Sepulveda, Pablo Vargas, Ana-Maria Lennon-Duménil, Peter van Endert, Thierry Capiod, Nicolas Demaurex, Guillaume Darrasse-Jèze, Bénédicte Manoury
Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158404/cd1b-restricted-gem-t-cell-responses-are-modulated-by-mycobacterium-tuberculosis-mycolic-acid-meromycolate-chains
#4
Andrew Chancellor, Anna S Tocheva, Chris Cave-Ayland, Liku Tezera, Andrew White, Juma'a R Al Dulayymi, John S Bridgeman, Ivo Tews, Susan Wilson, Nikolai M Lissin, Marc Tebruegge, Ben Marshall, Sally Sharpe, Tim Elliott, Chris-Kriton Skylaris, Jonathan W Essex, Mark S Baird, Stephan Gadola, Paul Elkington, Salah Mansour
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29155319/impact-of-human-leukocyte-antigen-hla-alleles-on-outcomes-of-allogeneic-transplantation-for-b-cell-non-hodgkin-lymphomas-a-center-for-international-blood-and-marrow-transplant-research-analysis
#5
Basem M William, Tao Wang, Michael D Haagenson, Katharina Fleischhauer, Michael Verneris, Katharine C Hsu, Marcos J de Lima, Marcelo Fernandez-Viña, Stephen R Spellman, Stephanie J Lee, Brian T Hill
Even in the modern era of targeted therapies, allogeneic hematopoietic stem cell transplantation (allo-HCT) can offer a chance of extended survival in B-cell non-Hodgkin lymphoma (B-NHL) patients who relapse after, or are deemed ineligible for, autologous transplantation. A better understanding of the factors influencing the graft vs lymphoma (GVL) response would be useful in identifying B-NHL patients who may benefit from allo-HCT. Based on prior single-center reports, we hypothesized that certain HLA alleles, or haplotypes, may be associated with superior GVL, compared to others, after allo-HCT...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29154744/generation-and-characterization-of-a-novel-candidate-gene-therapy-and-vaccination-vector-based-on-human-species-d-adenovirus-type-56
#6
Margaret R Duffy, Julio Alonso-Padilla, Lijo John, Naresh Chandra, Selina Khan, Monika Z Ballmann, Agnieszka Lipiec, Evert Heemskerk, Jerome Custers, Niklas Arnberg, Menzo Havenga, Andrew H Baker, Angelique Lemckert
The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i...
November 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29154369/hepatitis-e-virus-infection
#7
REVIEW
Nassim Kamar, Jacques Izopet, Nicole Pavio, Rakesh Aggarwal, Alain Labrique, Heiner Wedemeyer, Harry R Dalton
Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces...
November 16, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#8
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#9
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146922/molecular-definition-of-multiple-sites-of-antibody-inhibition-of-malaria-transmission-blocking-vaccine-antigen-pfs25
#10
Stephen W Scally, Brandon McLeod, Alexandre Bosch, Kazutoyo Miura, Qi Liang, Sean Carroll, Sini Reponen, Ngan Nguyen, Eldar Giladi, Sebastian Rämisch, Vidadi Yusibov, Allan Bradley, Franck Lemiale, William R Schief, Daniel Emerling, Paul Kellam, C Richter King, Jean-Philippe Julien
The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#11
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/29146232/parathyroidectomy-in-patients-with-chronic-kidney-disease-impacts-of-different-techniques-on-the-biochemical-and-clinical-evolution-of-secondary-hyperparathyroidism
#12
Roxana de Fátima Camelo Albuquerque, Cinthia Esbrile Moraes Carbonara, Rita de Cássia T Martin, Luciene Machado Dos Reis, Climério Pereira do Nascimento, Sérgio Samir Arap, Rosa M A Moysés, Vanda Jorgetti, Fábio L M Montenegro, Rodrigo Bueno de Oliveira
BACKGROUND: Parathyroidectomy (PTx) decreases the mortality rate of refractory secondary hyperparathyroidism (rSHP) due to chronic kidney disease. A consensus regarding which techniques of PTx are associated with better outcomes is not available. The aims of this study are to evaluate the clinical and laboratory evolution of 49 hemodialysis patients with rSHP who underwent PTx using different techniques. METHODS: Patients underwent subtotal PTx (sub-PTx) or total PTx with autotransplantation (AT) of 45 (PTx-AT45) or 90 parathyroid fragments (PTx-AT90) and were followed for 12 months...
November 13, 2017: Surgery
https://www.readbyqxmd.com/read/29143908/the-hp10-taenia-monoclonal-antibody-based-elisa-detects-a-similar-protein-in-the-vesicular-fluid-of-taenia-hydatigena
#13
Maria M Cortez, Glenda C Rojas, R Michael E Parkhouse
Diagnosis of Taenia solium cysticercosis in endemic rural communities depends on serological tests, as typically there is no access to imaging facilities. The HP10 antigen ELISA (HP10 Ag ELISA), which detects a high molecular weight secreted protein of viable metacestodes, has been employed for the diagnosis of both human and porcine cysticercosis in such communities. In this communication, we formally demonstrate that the HP10 Ag ELISA, already known to function for the detection of T. saginata and T. solium cysticercosis, also detects a similar high molecular weight antigen of T...
November 16, 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/29143375/an-immunoinformatics-approach-to-define-t-cell-epitopes-from-polyketide-and-non-ribosomal-peptide-synthesis-proteins-of-mycobacterium-tuberculosis-as-potential-vaccine-candidates
#14
S Dhivya, V Baskar, S R Kumar, R Sathishkumar
The role of polyketide and non-ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty-one proteins from polyketide and non-ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides...
November 16, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29142506/detection-of-circulating-natural-antibodies-to-inflammatory-cytokines-in-type-2-diabetes-and-clinical-significance
#15
Weiyi Cai, Cailing Qiu, Hongyu Zhang, Xiangyun Chen, Xuan Zhang, Qingyong Meng, Jun Wei
Background: Inflammatory cytokines have been demonstrated to be involved in developing insulin resistance and type-2 diabetes (T2D). Natural antibodies in the circulation have protective effects on common diseases in humans. The present study was thus designed to test the hypothesis that natural antibodies against inflammatory cytokines could be associated with T2D. Methods: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG against peptide antigens derived from interleukin 1α (IL1α), IL1β, IL6, IL8 and tumor necrosis factor-α (TNF-α) in 200 patients with T2D and 220 control subjects...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29139030/potential-risk-factors-for-reactive-arthritis-and-persistence-of-symptoms-at-2%C3%A2-years-a-case-control-study-with-longitudinal-follow-up
#16
Helga Raquel Garcia Ferrer, Alexander Azan, Isa Iraheta, Joan Von Feldt, Luis R Espinoza, Julia Manasson, Jose U Scher, Abraham Garcia Kutzbach, Alexis Ogdie
The objective of the study is to determine the risk factors for the development of reactive arthritis (ReA) and examine the factors associated with the persistence of symptoms. Patients with a new diagnosis of ReA and controls with a gastrointestinal (GI), urogenital, or sexually transmitted infection in the 3-6 months prior to study entry were prospectively enrolled in Guatemala City. ReA patients fulfilled the Assessment in Spondyloarthritis International Society criteria for peripheral spondyloarthropathy (SpA)...
November 14, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29137242/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#17
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136163/ascaris-suum-infection-down-regulates-inflammatory-pathways-in-the-pig-intestine-in-vivo-and-in-human-dendritic-cells-in-vitro
#18
Helene L E Midttun, Nathalie Acevedo, Per Skallerup, Sara Almeida, Kerstin Skovgaard, Lars Andresen, Søren Skov, Luis Caraballo, Irma van Die, Claus B Jørgensen, Merete Fredholm, Stig M Thamsborg, Peter Nejsum, Andrew R Williams
Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost one billion people. Ascaris spp. is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad down-regulation of genes encoding cytokines and antigen-processing and co-stimulatory molecules...
November 9, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29134204/latent-membrane-protein-1-is-a-novel-determinant-of-epstein-barr-virus-genome-persistence-and-reactivation
#19
Elizabeth A Caves, Rachel M Butch, Sarah A Cook, Laura R Wasil, Chen Chen, Yuanpu Peter Di, Nara Lee, Kathy H Y Shair
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that persistently infects humans, with nearly 95% seropositivity in adults. Infection in differentiating epithelia is permissive, but EBV-associated nasopharyngeal carcinoma (NPC) tumors harbor a clonal and nonproductive latent infection. However, in explanted NPC cultures and epithelial cell lines, episomal EBV genomes are frequently lost. The resulting unstable infection has hampered efforts to study the determinants of EBV persistence and latency in epithelial oncogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29133460/elevated-hur-in-pancreas-promotes-a-pancreatitis-like-inflammatory-microenvironment-that-facilitates-tumor-development
#20
Weidan Peng, Narumi Furuuchi, Ludmila Aslanukova, Yu-Hung Huang, Samantha Z Brown, Wei Jiang, Sankar Addya, Vikalp Vishwakarma, Erika Peters, Jonathan R Brody, Dan A Dixon, Janet A Sawicki
Human antigen R (ELAVL1, HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes post-transcriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR overexpressing pancreas displays a fibro-inflammatory response and other pathological features characteristic of chronic pancreatitis...
November 13, 2017: Molecular and Cellular Biology
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