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antigen-presentation

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https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#1
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811364/mechanosensing-drives-acuity-of-%C3%AE-%C3%AE-t-cell-recognition
#2
Yinnian Feng, Kristine N Brazin, Eiji Kobayashi, Robert J Mallis, Ellis L Reinherz, Matthew J Lang
T lymphocytes use surface [Formula: see text] T-cell receptors (TCRs) to recognize peptides bound to MHC molecules (pMHCs) on antigen-presenting cells (APCs). How the exquisite specificity of high-avidity T cells is achieved is unknown but essential, given the paucity of foreign pMHC ligands relative to the ubiquitous self-pMHC array on an APC. Using optical traps, we determine physicochemical triggering thresholds based on load and force direction. Strikingly, chemical thresholds in the absence of external load require orders of magnitude higher pMHC numbers than observed physiologically...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28808328/light-guided-in-vivo-activation-of-innate-immune-cells-with-photocaged-tlr-2-6-agonist
#3
Keun Ah Ryu, Bethany McGonnigal, Troy Moore, Tawnya Kargupta, Rock J Mancini, Aaron P Esser-Kahn
The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800929/directing-t-cell-fate-how-thymic-antigen-presenting-cells-coordinate-thymocyte-selection
#4
REVIEW
Elise R Breed, S Thera Lee, Kristin A Hogquist
The development of a self-tolerant and effective T cell receptor repertoire is dependent on interactions coordinated by various antigen presenting cells (APC) within the thymus. T cell receptor-self-peptide-MHC interactions are essential for determining T cell fate, however different cytokine and co-stimulatory signals provided by the diverse APCs within the thymus are also critical. Here, we outline the different localization and functional capabilities of thymic APCs. We also discuss how these distinct APCs work collectively to facilitate the establishment of a diverse T cell receptor repertoire that is tolerant to an array of different self-antigens...
August 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28799643/sebocytes-contribute-to-skin-inflammation-by-promoting-the-differentiation-of-th17-cells
#5
M Mattii, M Lovászi, N Garzorz, A Atenhan, M Quaranta, F Lauffer, A Konstantinow, M Küpper, C C Zouboulis, L Kemeny, K Eyerich, C B Schmidt-Weber, D Törőcsik, S Eyerich
BACKGROUND: The main function of sebocytes is considered to be the lipid production for moisturizing the skin. However, it became recently apparent that sebocytes release chemokines and cytokines and respond to pro-inflammatory stimuli as well as presence of bacteria. OBJECTIVES: To analyze the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and IL-17 were performed on acne sections and healthy skin...
August 11, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28798750/heme-oxygenase-1-expression-contributes-to-the-immunoregulation-induced-by-fasciola-hepatica-and-promotes-infection
#6
Paula Carasi, Ernesto Rodríguez, Valeria da Costa, Sofía Frigerio, Natalie Brossard, Verónica Noya, Carlos Robello, Ignacio Anegón, Teresa Freire
Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28798749/enhancement-of-adjuvant-functions-of-natural-killer-t-cells-using-nanovector-delivery-systems-application-in-anticancer-immune-therapy
#7
REVIEW
Reem Ghinnagow, Luis Javier Cruz, Elodie Macho-Fernandez, Christelle Faveeuw, François Trottein
Type I natural killer T (NKT) cells have gained considerable interest in anticancer immune therapy over the last decade. This "innate-like" T lymphocyte subset has the unique ability to recognize foreign and self-derived glycolipid antigens in association with the CD1d molecule expressed by antigen-presenting cells. An important property of these cells is to bridge innate and acquired immune responses. The adjuvant function of NKT cells might be exploited in the clinics. In this review, we discuss the approaches currently being used to target NKT cells for cancer therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28798047/mtor-regulates-metabolic-adaptation-of-apcs-in-the-lung-and-controls-the-outcome-of-allergic-inflammation
#8
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28795218/atopy-and-prostate-cancer-is-there-a-link-between-circulating-levels-of-ige-and-psa-in-humans
#9
Mieke Van Hemelrijck, Sophia N Karagiannis, Sabine Rohrmann
BACKGROUND: Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005-2006...
August 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28794879/human-papillomavirus-driven-immune-deviation-challenge-and-novel-opportunity-for-immunotherapy
#10
REVIEW
Sigrun Smola, Connie Trimble, Peter L Stern
It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer...
June 2017: Therapeutic Advances in Vaccines
https://www.readbyqxmd.com/read/28794505/differential-transcriptome-of-tolerogenic-versus-inflammatory-dendritic-cells-points-to-modulated-t1d-genetic-risk-and-enriched-immune-regulation
#11
T Nikolic, N J C Woittiez, A van der Slik, S Laban, A Joosten, C Gysemans, C Mathieu, J J Zwaginga, B Koeleman, B O Roep
Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD3/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators...
August 10, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28794025/retrovirus-based-virus-like-particle-immunogenicity-and-its-modulation-by-toll-like-receptor-activation
#12
Fabien Pitoiset, Thomas Vazquez, Beatrice Levacher, Djamel Nehar-Belaid, Nicolas Dérian, James Vigneron, David Klatzmann, Bertrand Bellier
Retrovirus-derived virus-like particles (VLPs) are particularly interesting vaccine platforms as they trigger efficient humoral and cellular immune responses and can be used to display heterologous antigens. In this study, we characterized the intrinsic immunogenicity of VLPs and investigated their possible adjuvantization by incorporation of toll-like receptor (TLR) ligands. We designed a non-coding single-stranded RNA (ncRNA) that could be encapsidated by VLPs and induce TLR7/8-signaling. We found that VLPs efficiently induce in vitro dendritic cell activation, which can be improved by ncRNA encapsidation (ncRNAVLPs)...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28791124/combining-dendritic-cells-and-b-cells-for-presentation-of-oxidised-tumour-antigens-to-cd8-t-cells
#13
Melanie L Grant, Nicholas Shields, Silke Neumann, Katrin Kramer, Andrea Bonato, Christopher Jackson, Margaret A Baird, Sarah L Young
The dendritic cell (DC) is the foremost antigen-presenting cell (APC) for ex vivo expansion of tumour-specific patient T cells. Despite marked responses in some patients following reinfusion of DC-activated autologous or HLA-matched donor T cells, overall response rates remain modest in solid tumours. Furthermore, most studies aim to generate immune responses against defined tumour-associated antigens (TAA), however, meta-analysis reveals that those approaches have less clinical success than those using whole tumour cells or their components...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28790822/complement-c3-dependent-uptake-of-targeted-liposomes-into-human-macrophages-b-cells-dendritic-cells-neutrophils-and-mdscs
#14
Alexandra Francian, Kristine Mann, Max Kullberg
Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presenting cells, including dendritic cells, macrophages, and B cells, initiate immune recognition of tumor antigen by displaying antigen to effector cells. Countering this immune stimulation are immunosuppressive cells which include M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells (MDSCs). To create effective cancer immunotherapies, it is critical that we can target these important cell types of the immune system with immunostimulatory compounds...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28790345/oleate-but-not-stearate-induces-the-regulatory-phenotype-of-myeloid-suppressor-cells
#15
Hao Wu, Carl Weidinger, Franziska Schmidt, Jacqueline Keye, Marie Friedrich, Cansu Yerinde, Gerald Willimsky, Zhihai Qin, Britta Siegmund, Rainer Glauben
Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790195/the-tyrosine-phosphatase-shp-1-promotes-t-cell-adhesion-by-activating-the-adaptor-protein-crkii-in-the-immunological-synapse
#16
Inbar Azoulay-Alfaguter, Marianne Strazza, Michael Peled, Hila K Novak, James Muller, Michael L Dustin, Adam Mor
The adaptor protein CrkII regulates T cell adhesion by recruiting the guanine nucleotide exchange factor C3G, an activator of Rap1. Subsequently, Rap1 stimulates the integrin LFA-1, which leads to T cell adhesion and interaction with antigen-presenting cells (APCs). The adhesion of T cells to APCs is critical for their proper function and education. The interface between the T cell and the APC is known as the immunological synapse. It is characterized by the specific organization of proteins that can be divided into central supramolecular activation clusters (c-SMACs) and peripheral SMACs (p-SMACs)...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28789965/application-of-polyploid-adeno-associated-virus-vectors-for-transduction-enhancement-and-neutralizing-antibody-evasion
#17
Zheng Chai, Junjiang Sun, Kelly Michelle Rigsbee, Mei Wang, R Jude Samulski, Chengwen Li
Adeno-associated virus (AAV) vectors have been used successfully in clinical trials for patients with hemophilia or blindness, but pre-existing neutralizing antibodies (Nab) are common in the general population and exclude many patients from clinical trials. Exploration of effective strategies to enhance AAV transduction and escape from Nab activity is still imperative. Previous studies have shown the compatibility of capsids from AAV serotypes and homology of recognition sites of AAV Nab located on different capsid subunits from one virion...
August 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28789924/constitutive-interaction-between-4-1bb-and-4-1bbl-on-murine-lps-activated-bone-marrow-dendritic-cells-masks-detection-of-4-1bbl-by-tks-1-but-not-19h3-antibody
#18
Achire N Mbanwi, Gloria H Y Lin, Kuan Chung Wang, Tania H Watts
4-1BB is a TNFR family member associated with NF-κB mediated survival signaling. 4-1BB is widely expressed on activated cells of the immune system, including activated T cells, NK cells and dendritic cells. Its ligand, 4-1BBL, is transiently expressed on activated antigen presenting cells and at low levels on activated T cells. Although 4-1BBL-deficient mice clearly demonstrate a role for 4-1BBL in CD8 T cell responses to viruses such as influenza, 4-1BBL can be difficult to detect following infection of mice...
August 5, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28789525/direct-loading-of-itep-delivered-ctl-epitopes-onto-mhc-class-i-complexes-on-the-dendritic-cell-surface
#19
Shuyun Dong, Peng Wang, Peng Zhao, Mingnan Chen
Cytotoxic T lymphocyte (CTL)-mediated immune responses are the primary defense mechanism against cancer and infection. CTL epitope peptides have been used as vaccines to boost CTL responses; however, the efficacy of these peptides is suboptimal. Under current vaccine formulation and delivery strategies, these vaccines are delivered into and processed inside antigen presenting cells such as dendritic cells (DCs). However, the intracellular process is not efficient, which at least partially contributes to the suboptimal efficacy of the vaccines...
August 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28783722/identification-of-essential-genes-for-cancer-immunotherapy
#20
Shashank J Patel, Neville E Sanjana, Rigel J Kishton, Arash Eidizadeh, Suman K Vodnala, Maggie Cam, Jared J Gartner, Li Jia, Seth M Steinberg, Tori N Yamamoto, Anand S Merchant, Gautam U Mehta, Anna Chichura, Ophir Shalem, Eric Tran, Robert Eil, Madhusudhanan Sukumar, Eva Perez Guijarro, Chi-Ping Day, Paul Robbins, Steve Feldman, Glenn Merlino, Feng Zhang, Nicholas P Restifo
Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8(+) T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas...
August 7, 2017: Nature
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