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"Cross-presentation"

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https://www.readbyqxmd.com/read/29760705/induction-of-cytotoxic-t-lymphocyte-responses-upon-subcutaneous-administration-of-a-subunit-vaccine-adjuvanted-with-an-emulsion-containing-the-toll-like-receptor-3-ligand-poly-i-c
#1
Signe Tandrup Schmidt, Gabriel Kristian Pedersen, Malene Aaby Neustrup, Karen Smith Korsholm, Thomas Rades, Peter Andersen, Camilla Foged, Dennis Christensen
There is an unmet medical need for new subunit vaccines that induce cytotoxic T-lymphocyte (CTL) responses to prevent infection with a number of pathogens. However, stimulation of CTL responses via clinically acceptable subcutaneous (s.c.) and intramuscular (i.m.) injection is challenging. Recently, we designed a liposomal adjuvant [cationic adjuvant formulation (CAF)09] composed of the cationic lipid dimethyldioctadecylammonium (DDA) bromide, a synthetic monomycoloyl glycerol analog and polyinosinic:polycytidylic acid, which induce strong CTL responses to peptide and protein antigens after intraperitoneal administration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755461/efficient-uptake-of-recombinant-lipidated-survivin-by-antigen-presenting-cells-initiates-antigen-cross-presentation-and-antitumor-immunity
#2
Chen-Yi Chiang, Yi-Jyun Chen, Chiao-Chieh Wu, Shih-Jen Liu, Chih-Hsiang Leng, Hsin-Wei Chen
Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their toll-like receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli -based system...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29743717/integrating-oncolytic-viruses-in-combination-cancer-immunotherapy
#3
REVIEW
Praveen K Bommareddy, Megha Shettigar, Howard L Kaufman
Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments...
May 9, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29706455/extrinsic-phagocyte-dependent-sting-signaling-dictates-the-immunogenicity-of-dying-cells
#4
Jeonghyun Ahn, Tianli Xia, Ailem Rabasa Capote, Dillon Betancourt, Glen N Barber
The ability of dying cells to activate antigen-presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here, we show that engulfed cells containing cytosolic double-stranded DNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs via extrinsic STING (stimulator of interferon genes) signaling, to promote antigen cross-presentation. In the absence of STING agonists, dying cells were ineffectual in the stimulation of APCs in trans. Cytosolic STING activators, including CDNs, constitute cellular danger-associated molecular patterns (DAMPs) only generated by viral infection or following DNA damage events that rendered tumor cells highly immunogenic...
April 17, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29676785/sustained-cross-presentation-capacity-of-murine-splenic-dendritic-cell-subsets-in-vivo
#5
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Ferry Ossendorp
An exclusive feature of dendritic cells (DCs) is their ability to cross-present exogenous antigens in MHC class I molecules. We analyzed the fate of protein antigen in antigen presenting cell (APC) subsets after uptake of naturally formed antigen-antibody complexes in vivo. We observed that murine splenic DC subsets were able to present antigen in vivo for at least a week. After ex vivo isolation of four APC subsets, the presence of antigen in the storage compartments was visualized by confocal microscopy. Although all APC subsets stored antigen for many days, their ability and kinetics in antigen presentation was remarkably different...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29675543/improved-vaccine-induced-immune-responses-via-a-ros-triggered-nanoparticle-based-antigen-delivery-system
#6
Xiaoyu Liang, Jianwei Duan, Xuanling Li, Xiaowei Zhu, Youlu Chen, Xiaoli Wang, Hongfan Sun, Deling Kong, Chen Li, Jing Yang
Subunit vaccines that are designed based on recombinant antigens or peptides have shown promising potential as viable substitutes for traditional vaccines due to their better safety and specificity. However, the induction of adequate in vivo immune responses with appropriate effectiveness remains a major challenge for vaccine development. More recently, the implementation of a nanoparticle-based antigen delivery system has been considered a promising approach to improve the in vivo efficacy for subunit vaccine development...
April 20, 2018: Nanoscale
https://www.readbyqxmd.com/read/29669333/the-role-of-proteasome-inhibitor-mg132-in-2-4-dinitrofluorobenzene-induced-atopic-dermatitis-in-nc-nga-mice
#7
Kozo Ohkusu-Tsukada, Daiki Ito, Kimimasa Takahashi
BACKGROUND: Although immunosuppressants for therapy of atopic dermatitis (AD) are still being sought, proteasome inhibitors are also potential candidates for the treatment of AD. Proteasome inhibitors exert various effects by blocking proteasomal degradation and help regulate processes such as apoptosis induction via caspase-9, cell cycle progression via cyclins, NF-κB inactivation via IκB, and downregulation of antigen cross-presentation. The cells targeted by proteasome inhibitors are therefore activated cells undergoing proliferation or differentiation, and antigen-presenting cells carrying out protein degradation...
April 18, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29661776/targeting-the-leukemia-antigen-pr1-with-immunotherapy-for-the-treatment-of-multiple-myeloma
#8
Gheath Alatrash, Alexander A Perakis, Celine Kerros, Haley L Peters, Pariya Sukhumalchandra, Mao Zhang, Haroon Jakher, Madhushree Zope, Rebecca S Patenia, Anna Sergeeva, Shuhua Yi, Ken H Young, Anne V Philips, Amanda C Herrmann, Haven R Garber, Na Qiao, Jinsheng Weng, Lisa S St John, Sijie Lu, Karen Clise-Dwyer, Elizabeth A Mittendorf, Qing Ma, Jeffrey J Molldrem
PURPOSE: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. Since multiple myeloma (MM) is derived from B cells, we investigated whether MM is also capable of PR1 cross-presentation and subsequently capable of being targeted using PR1 immunotherapies...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29628306/tumor-resident-dendritic-cells-and-macrophages-modulate-the-accumulation-of-tcr-engineered-t-cells-in-melanoma
#9
Alastair Hotblack, Angelika Holler, Alice Piapi, Sophie Ward, Hans J Stauss, Clare L Bennett
Ongoing clinical trials explore T cell receptor (TCR) gene therapy as a treatment option for cancer, but responses in solid tumors are hampered by the immunosuppressive microenvironment. The production of TCR gene-engineered T cells requires full T cell activation in vitro, and it is currently unknown whether in vivo interactions with conventional dendritic cells (cDCs) regulate the accumulation and function of engineered T cells in tumors. Using the B16 melanoma model and the inducible depletion of CD11c+ cells in CD11c...
March 16, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29628230/chitosan-stabilized-nasal-emulsion-delivery-system-for-effective-humoral-and-cellular-response-against-recombinant-tetravalent-dengue-antigen
#10
Sravanthi Vemireddy, Preethi Pallavi M C, Sampath Kumar Halmuthur M
Nasal vaccine delivery systems are emerging alternatives to the conventional sub unit vaccine delivery systems owing to their ability to stimulate potent antigen specific humoral and cellular immune responses. Additional virtue of nasal delivery is its close proximity of immune cells to external epithelial layer which is the route of entry to pathogens. Toxicity of emulsion based vaccine delivery systems may be attributed to the presence of high quantities of surfactants used for stabilizing the emulsions. A safer approach would be to reduce physiologically unwanted surfactant burden in the emulsion to the bare limit to necessity...
June 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29618478/nadph-oxidase-activation-regulates-apoptotic-neutrophil-clearance-by-murine-macrophages
#11
Juhi Bagaitkar, Jing Huang, Melody Yue Zeng, Nancy K Pech, Darlene A Monlish, Lizet J Perez-Zapata, Irina Miralda, Laura G Schuettpelz, Mary C Dinauer
The phagocyte NADPH oxidase generates superoxide, the precursor to reactive oxygen species (ROS) that have both antimicrobial and immunoregulatory functions. Inactivating mutations in NADPH oxidase alleles cause chronic granulomatous disease (CGD), characterized by enhanced susceptibility to life-threatening microbial infections and inflammatory disorders, and hypomorphic NADPH oxidase alleles are associated with autoimmunity. Impaired apoptotic cell (AC) clearance is implicated as an important contributing factor in chronic inflammation and autoimmunity, but the role of NADPH oxidase-derived ROS in this process is incompletely understood...
April 4, 2018: Blood
https://www.readbyqxmd.com/read/29595473/topoisomerase-vi-senses-and-exploits-both-dna-crossings-and-bends-to-facilitate-strand-passage
#12
Timothy J Wendorff, James M Berger
Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP...
March 29, 2018: ELife
https://www.readbyqxmd.com/read/29594331/extracellular-vesicle-mediated-mhc-cross-dressing-in-immune-homeostasis-transplantation-infectious-diseases-and-cancer
#13
REVIEW
Furong Zeng, Adrian E Morelli
Eukaryotic cells employ different types of extracellular vesicles (EVs) to exchange proteins, mRNAs, non-coding regulatory RNAs, carbohydrates, and lipids. Cells of the immune system, in particular antigen (Ag)-presenting cells (APCs), acquire major histocompatibility complex (MHC) class I and II molecules loaded with antigenic peptides from leukocytes and tissue parenchymal and stromal cells, through a mechanism known as MHC cross-dressing. Increasing evidence indicates that cross-dressing of APCs with pre-formed Ag-peptide/MHC complexes (pMHCs) is mediated via passage of clusters of EVs with characteristics of exosomes...
March 28, 2018: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29575556/development-of-a-vaccine-based-on-bacteria-mimicking-tumor-cells-coated-with-novel-engineered-tlr2-ligands
#14
Takashi Akazawa, Toshimitsu Ohashi, Viskam Wijewardana, Kikuya Sugiura, Norimitsu Inoue
For a successful tumor vaccine, it is necessary to develop effective immuno-adjuvants and identify specific tumor antigens. Tumor cells obtained from surgical or biopsy tissues are a good source of tumor antigens but, unlike bacteria, they do not induce strong immune responses. Here, we designed two novel lipopeptides that coat tumor cell surfaces and mimic bacterial components. Tumor cells coated with these lipopeptides (called bacteria-mimicking tumor cells (BMTCs)) were prepared and their efficacy as a tumor vaccine examined...
March 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/29563123/murine-cmv-induces-type-1-ifn-that-impairs-differentiation-of-mdscs-critical-for-transplantation-tolerance
#15
Anil Dangi, Lei Zhang, Xiaomin Zhang, Xunrong Luo
Clinical tolerance without immunosuppression has now been achieved for organ transplantation, and its scope will likely continue to expand. In this context, a previously understudied and now increasingly relevant area is how microbial infections might affect the efficacy of tolerance. A highly prevalent and clinically relevant posttransplant pathogen is cytomegalovirus (CMV). Its impact on transplantation tolerance and graft outcomes is not well defined. Employing a mouse model of CMV (MCMV) infection and allogeneic pancreatic islet transplantation in which donor-specific tolerance was induced by infusing donor splenocytes rendered apoptotic by treatment with ethylenecarbodiimide, we investigated the effect of CMV infection on transplantation tolerance induction...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29559473/erap1-dependent-antigen-cross-presentation-determines-efficacy-of-adoptive-t-cell-therapy-in-mice
#16
Karin Schmidt, Christin Keller, Anja A Kühl, Ana Textor, Ulrike Seifert, Thomas Blankenstein, Gerald Willimsky, Peter-Michael Kloetzel
Cytotoxic T lymphocytes can reject established tumors if their target peptide is efficiently presented by major histocompatibility complex class I molecules (pMHC-I) on the surface of cancerous cells. Therapeutic success upon adoptive T cell transfer (ATT), however, requires additional cross-presentation of the same pMHC-I on non-cancerous cells. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that customizes the N-terminus of proteasome-generated peptides so they can be loaded onto MHC-I molecules in the endoplasmic reticulum (ER)...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29555965/mechanisms-underlying-the-lack-of-endogenous-processing-and-clip-mediated-binding-of-the-invariant-chain-by-hla-dp-84gly
#17
Mark Anczurowski, Yuki Yamashita, Munehide Nakatsugawa, Toshiki Ochi, Yuki Kagoya, Tingxi Guo, Chung-Hsi Wang, Muhammed A Rahman, Kayoko Saso, Marcus O Butler, Naoto Hirano
While the principles of classical antigen presentation via MHC class II are well-established, the mechanisms for the many routes of cross-presentation by which endogenous antigens become associated with class II molecules are not fully understood. We have recently demonstrated that the single amino acid polymorphism HLA-DPβ84Gly (DP84Gly ) is critical to abrogate class II invariant chain associated peptide (CLIP) region-mediated binding of invariant chain (Ii) to DP, allowing endoplasmic reticulum (ER)-resident endogenous antigens to constitutively associate with DP84Gly such as DP4...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29546878/inflammation-induces-two-types-of-inflammatory-dendritic-cells-in-inflamed-lymph-nodes
#18
Jiyoun Min, Dongchan Yang Sung, Mirang Kim, Keeok Haam, Anji Yoo, Jae-Hoon Choi, Barbara U Schraml, Yong Sung Kim, Dongsup Kim, Suk-Jo Kang
The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64+ CD11c+ MHCII+ inflammatory DCs...
March 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29507342/cancer-associated-fibroblasts-induce-antigen-specific-deletion-of-cd8-t-cells-to-protect-tumour-cells
#19
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
https://www.readbyqxmd.com/read/29507107/clec9a-dendritic-cells-are-not-essential-for-antitumor-cd8-t-cell-responses-induced-by-poly-i-c-immunotherapy
#20
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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