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https://www.readbyqxmd.com/read/28317931/recruitment-of-bone-marrow-cd11b-gr-1-cells-by-polymeric-nanoparticles-for-antigen-cross-presentation
#1
Ya-Wun Yang, Wen-Hui Luo
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8(+) T cell responses via the CD11b(+)Gr(-)1(+) myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b(+)Gr-1(low)Ly-6C(high) and CD11b(+)Gr-1(high)Ly-6C(low) subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8(+) cells...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296410/a-light-responsive-nanoparticle-based-delivery-system-using-pheophorbide-a-graft-polyethyleneimine-for-dendritic-cell-based-cancer-immunotherapy
#2
Chuangnian Zhang, Ju Zhang, Gaona Shi, Huijuan Song, Shengbin Shi, Xiuyuan Zhang, Pingsheng Huang, Zhihong Wang, Weiwei Wang, Chun Wang, Deling Kong, Chen Li
In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8(+) T cell immune response for cancer immunotherapy. Pheophorbide-A, a hydrophobic photosensitizer, grafted with polyethyleneimine (PheoA-PEI) with endosome escape activity and near infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light...
March 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#3
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Fiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28287107/dying-cells-actively-regulate-adaptive-immune-responses
#4
REVIEW
Nader Yatim, Sean Cullen, Matthew L Albert
Dying cells have an important role in the initiation of CD8(+) T cell-mediated immunity. The cross-presentation of antigens derived from dying cells enables dendritic cells to present exogenous tissue-restricted or tumour-restricted proteins on MHC class I molecules. Importantly, this pathway has been implicated in multiple autoimmune diseases and accounts for the priming of tumour antigen-specific T cells. Recent data have revealed that in addition to antigen, dying cells provide inflammatory and immunogenic signals that determine the efficiency of CD8(+) T cell cross-priming...
March 13, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28277646/efficient-nanovaccine-delivery-in-cancer-immunotherapy
#5
Guizhi Zhu, Fuwu Zhang, Qianqian Ni, Gang Niu, Xiaoyuan Chen
Vaccines hold tremendous potential for cancer immunotherapy by treating the immune system. Subunit vaccines, including molecular adjuvants and cancer-associated antigens or cancer-specific neoantigens, can elicit potent antitumor immunity. However, subunit vaccines have shown limited clinical benefit in cancer patients, which is in part attributed to inefficient vaccine delivery. In this Perspective, we discuss vaccine delivery by synthetic nanoparticles or naturally derived nanoparticles for cancer immunotherapy...
March 9, 2017: ACS Nano
https://www.readbyqxmd.com/read/28277277/immunoregulation-of-dendritic-cell-subsets-by-inhibitory-receptors-in-urothelial-cancer
#6
Mathieu F Chevalier, Perrine Bohner, Claire Pieraerts, Benoit Lhermitte, Jolanta Gourmaud, Antoine Nobile, Samuel Rotman, Valerie Cesson, Virginie Martin, Anne-Sophie Legris, Florence Dartiguenave, Dalila Gharbi, Laurence De Leval, Daniel E Speiser, Denise Nardelli-Haefliger, Patrice Jichlinski, Laurent Derré
Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs...
October 27, 2016: European Urology
https://www.readbyqxmd.com/read/28270814/the-novel-toll-like-receptor-2-agonist-sup3-enhances-antigen-presentation-and-t-cell-activation-by-dendritic-cells
#7
Xueheng Guo, Ning Wu, Yingli Shang, Xin Liu, Tao Wu, Yifan Zhou, Xin Liu, Jiaoyan Huang, Xuebin Liao, Li Wu
Dendritic cells (DCs) are highly specialized antigen-presenting cells that play crucial roles in innate and adaptive immunity. Previous studies suggested that Toll-like receptor (TLR) agonists could be used as potential adjuvants, as activation of TLRs can boost DC-induced immune responses. TLR2 agonists have been shown to enhance DC-mediated immune responses. However, classical TLR2 agonists such as Pam3CSK4 are not stable enough in vivo, which limits their clinical applications. In this study, a novel structurally stable TLR2 agonist named SUP3 was designed...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270408/phenotypic-and-functional-consequences-of-different-isolation-protocols-on-skin-mononuclear-phagocytes
#8
Rachel A Botting, Kirstie M Bertram, Heeva Baharlou, Kerrie J Sandgren, James Fletcher, Jake W Rhodes, Hafsa Rana, Toby M Plasto, Xin Maggie Wang, Jake J K Lim, Laith Barnouti, Mark P Kohout, Tim Papadopoulos, Steve Merten, Norman Olbourne, Anthony L Cunningham, Muzlifah Haniffa, Andrew N Harman
Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined...
March 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28266658/targeted-antigen-delivery-to-dendritic-cells-elicits-robust-antiviral-t-cell-mediated-immunity-in-the-liver
#9
Julia Volckmar, Marcus Gereke, Thomas Ebensen, Peggy Riese, Lars Philipsen, Stefan Lienenklaus, Dirk Wohlleber, Robert Klopfleisch, Sabine Stegemann-Koniszewski, Andreas J Müller, Achim D Gruber, Percy Knolle, Carlos A Guzman, Dunja Bruder
Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257518/exposure-to-sequestered-self-antigens-in-vivo-is-not-sufficient-for-the-induction-of-autoimmune-diabetes
#10
Nobuyuki Ono, Kiichi Murakami, Olivia Chan, Håkan Hall, Alisha R Elford, Patty Yen, Thomas Calzascia, David M Spencer, Pamela S Ohashi, Salim Dhanji
Although the role of T cells in autoimmunity has been explored for many years, the mechanisms leading to the initial priming of an autoimmune T cell response remain enigmatic. The 'hit and run' model suggests that self-antigens released upon cell death can provide the initial signal for a self-sustaining autoimmune response. Using a novel transgenic mouse model where we could induce the release of self-antigens via caspase-dependent apoptosis. We tracked the fate of CD8+ T cells specific for the self-antigen...
2017: PloS One
https://www.readbyqxmd.com/read/28256637/ebola-virus-infection-kinetics-in-chimeric-mice-reveal-a-key-role-of-t-cells-as-barriers-for-virus-dissemination
#11
Anja Lüdtke, Paula Ruibal, David M Wozniak, Elisa Pallasch, Stephanie Wurr, Sabrina Bockholt, Sergio Gómez-Medina, Xiangguo Qiu, Gary P Kobinger, Estefanía Rodríguez, Stephan Günther, Susanne Krasemann, Juliana Idoyaga, Lisa Oestereich, César Muñoz-Fontela
Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b(+) DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103(+) DC subset...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#12
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28243087/cationic-liposomes-promote-antigen-cross-presentation-in-dendritic-cells-by-alkalizing-the-lysosomal-ph-and-limiting-the-degradation-of-antigens
#13
Jie Gao, Lukasz J Ochyl, Ellen Yang, James J Moon
Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation - the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8(+) T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I)...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28239619/evaluation-of-cross-presentation-in-bone-marrow-derived-dendritic-cells-in-vitro-and-splenic-dendritic-cells-ex-vivo-using-antigen-coated-beads
#14
Andrés Alloatti, Fiorella Kotsias, Eik Hoffmann, Sebastian Amigorena
Antigen presentation by MHC class I molecules, also referred to as cross-presentation, elicits cytotoxic immune responses. In particular, dendritic cells (DC) are the most proficient cross-presenting cells, since they have developed unique means to control phagocytic and degradative pathways. This protocol allows the evaluation of antigen cross-presentation both in vitro (by using bone marrow-derived DC) and ex vivo (by purifying CD8(+) DC from spleen after incorporation of particulate antigen) using ovalbumin (OVA)-coupled particles...
November 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28238782/vaccination-efficacy-with-marrow-mesenchymal-stem-cell-against-cancer-was-enhanced-under-simulated-microgravity
#15
Jing Li, Jun Chen, Xiuyu Li, Yanfang Qian
Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG)...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28228336/evaluation-of-hydrophobic-chitosan-based-particulate-formulations-of-porcine-reproductive-and-respiratory-syndrome-virus-vaccine-candidate-t-cell-antigens
#16
Helen Mokhtar, Lucia Biffar, Satyanarayana Somavarapu, Jean-Pierre Frossard, Sarah McGowan, Miriam Pedrera, Rebecca Strong, Jane C Edwards, Margarita Garcia-Durán, Maria Jose Rodriguez, Graham R Stewart, Falko Steinbach, Simon P Graham
PRRS control is hampered by the inadequacies of existing vaccines to combat the extreme diversity of circulating viruses. Since immune clearance of PRRSV infection may not be dependent on the development of neutralising antibodies and the identification of broadly-neutralising antibody epitopes have proven elusive, we hypothesised that conserved T cell antigens represent potential candidates for development of a novel PRRS vaccine. Previously we had identified the M and NSP5 proteins as well-conserved targets of polyfunctional CD8 and CD4 T cells...
February 3, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28213733/the-localization-of-a-heterologous-displayed-antigen-in-the-baculovirus-budded-virion-determines-the-type-and-strength-of-induced-adaptive-immune-response
#17
Eugenia Tavarone, Guido Nicolás Molina, Sabrina Amalfi, Andrea Peralta, Paula Molinari, Oscar Taboga
In the search of strategies of presentation of heterologous antigens to elicit humoral or cellular immune responses that modulate and properly potentiate each type of response, researchers have been studying baculovirus (BV) as vaccine vectors with promising results. For some years, several research groups explored different antigen presentation approaches using the BV AcNPV by expressing polypeptides on the surface of budded virions or by de novo synthesis of heterologous antigens by transduction of mammalian cells...
February 17, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28190711/cd8-t-cells-orchestrate-pdc-xcr1-dendritic-cell-spatial-and-functional-cooperativity-to-optimize-priming
#18
Anna Brewitz, Sarah Eickhoff, Sabrina Dähling, Thomas Quast, Sammy Bedoui, Richard A Kroczek, Christian Kurts, Natalio Garbi, Winfried Barchet, Matteo Iannacone, Frederick Klauschen, Waldemar Kolanus, Tsuneyasu Kaisho, Marco Colonna, Ronald N Germain, Wolfgang Kastenmüller
Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8(+) T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8(+) T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28185916/dna-vaccines-for-prostate-cancer
#19
REVIEW
Christopher D Zahm, Viswa Teja Colluru, Douglas G McNeel
DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines...
February 7, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28184299/the-role-of-cdc1s-in-vivo-cd8-t-cell-priming-through-cross-presentation
#20
REVIEW
Derek Theisen, Kenneth Murphy
The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells...
2017: F1000Research
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