Nucleic Acid-Based, mRNA-Targeted Therapeutics for Hematologic Malignancies
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
Two potential problems associated with the use of dsRNA are that it does not always act in a sequence-specific manner (45), and that exogenously introduced dsRNA can be a potent inducer of interferon and other effectors of innate immunity such as RNA-binding protein kinase (PKR) and RNase L (46,47), initiating a cascade of events that leads to widespread and nonspecific post-transcriptional gene silencing and ultimately cell death (48). This is conventionally thought to occur in the presence of longer dsRNA molecules (>30 bp) via the RNase L and the PKR and/or the toll-like receptor-3, but very new data challenge this dogma, at least in certain cell types. Two groups have recently identified short immunostimulatory sequence motifs that specifically induce an interferon response. Hornung et al. have identified short immunostimulatory sequence motifs (9 bp within a 19 bp fragment) that induce an interferon response in plasmacytoid dendritic cells via the toll-like receptor-7. Judge et al. have also identified sequence motifs that are immunostimulatory in primary human monocytes and plasmacytoid dendritic cells and suggest that the recognition happens within the endosomal pathway (49,50).
Probiotics as HRV Vaccine Adjuvants in Gn Pigs
Lijuan Yuan in Vaccine Efficacy Evaluation, 2022
In the following section, the findings from our serial studies of Gn pigs on the dose effects of the probiotic LA on innate and adaptive immune responses induced by the oral AttHRV vaccine are discussed (Yuan et al., 2013). We studied the effects of low dose (total 2.11 × 106CFU) and high dose (total 2.22 × 109CFU) LA on the intestinal and systemic 1) rotavirus-specific IFN-γ producing CD4+ and CD8+ T cell responses; 2) CD4+CD25+FoxP3+ and CD4+CD25−FoxP3+ Treg cell responses and the regulatory cytokine TGF-β and IL-10 production; 3) rotavirus-specific ASC and serum antibody responses; and 4) plasmacytoid dendritic cell (pDC) and conventional DC (cDC) frequencies, activation status, TLR expression, and cytokine production profile. The protective effect of the rotavirus vaccine against virus shedding and diarrhea was assessed in AttHRV-vaccinated Gn pigs fed with high, low, or no LA and challenged with the VirHRV.
Immunohistochemistry
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
AML (with or without maturation) is most often positive for pan-myeloid markers (CD13, CD33, MPO), CD11c, HLA-DR, CD34, and/or CD117, and may be positive for CD4, CD7, CD19 [cases associated with t(8;21)], CD56, CD64, and TdT. Acute promyelocytic leukemia (APL) is positive for pan-myeloid markers, CD64 (dim expression), and CD117, and may be positive for CD34 and CD2 in hypogranular variant (HLA-DR is negative in APL). Acute monoblastic leukemia is positive for monocytic markers (muramidase, CD68) and CD11c, and is often positive for CD2, CD4, CD56, and HLA-DR. Lymphoblasts express TdT, CD34, and lineage-specific markers depending on the type of leukemia [B-ALL is positive for CD19, CD22, and CD79a, and T-cell acute lymphoblastic lymphoma (T-ALL) is positive for pan-T-cell antigens and CD4/CD8 and may be positive for CD1a]. Mast cell disease is characterized by the expression of CD117, mast cell tryptase, and CD2. Langerhans cell lesions are typically positive for CD1a and S100. Blastic plasmacytoid dendritic cell neoplasm is positive for CD4, CD56, and CD123 (among other markers). Figures 4.20 through 4.25 shows the typical phenotypic profile of major types of acute leukemia..
An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial
Published in OncoImmunology, 2020
Julie Charles, Laurence Chaperot, Dalil Hannani, Juliana Bruder Costa, Isabelle Templier, Sabiha Trabelsi, Hugo Gil, Anaick Moisan, Virginie Persoons, Harald Hegelhofer, Edith Schir, Jean-Louis Quesada, Christophe Mendoza, Caroline Aspord, Olivier Manches, Pierre G. Coulie, Amir Khammari, Brigitte Dreno, Marie-Thérèse Leccia, Joel Plumas
With the advent of antibodies against immune checkpoints, cancer treatment entered in a new era. However, despite the clinical benefit observed in a large series of cancer indications, few patients respond to monotherapy. Thus, to increase the proportion of patients that could benefit from ICI, many clinical trials are conducted that combine these drugs with other treatments such as chemotherapy, targeted therapy or radiotherapy.23 Since ICI efficacy has been shown to depend on the presence of preexisting antitumor T cells, its combination with antitumor vaccination represents an attractive therapeutic approach.10 Vaccination with tumor-specific antigens can prime antitumor T cells whose restimulation can then be boosted by ICI. Moreover, it ought to increase the ratio between antitumor T cells and antimicrobial or antiself T cells, decreasing the autoimmune and inflammatory side effects of ICI. Diverse vaccine platforms can be used for therapeutic vaccination including proteins/peptides, RNA or DNA, viral-vector-based, tumor cells or dendritic cells-based vaccines.24 Among dendritic cells, plasmacytoid dendritic cells are of great interest.13 In murine models, PDC that were properly loaded with tumor antigens and activated induced strong CTL responses and tumor regression.17,25
Plasmacytoid dendritic cells and asthma: a review of current knowledge
Published in Expert Review of Respiratory Medicine, 2020
Yang Xi, John W. Upham
Plasmacytoid dendritic cells (pDC), a relatively rare cell type, have been well known for their specialized capacity to produce type I interferons (IFN-I) and also IFN-III following viral infections [2]. It has become increasingly recognized that alterations in pDC function contribute to the pathogenesis of virus infections and immune-mediated diseases. Among circulating leukocytes, pDC are responsible for the majority of IFN-3]. In people with asthma, multiple investigators have reported that pDC numbers and function are altered compared to pDC from healthy individuals [4]. Low number of circulating pDC during infancy is a risk factor for subsequent severe respiratory tract infections, wheezing, and a diagnosis of asthma by age 5 years [5]. Virus infections, especially those caused by HRV, are the most common triggers for acute asthma exacerbations. It has been proposed that deficient IFN-I/III production in asthma might predispose to viral-induced asthma exacerbations, though the role of pDC in this situation requires further research. In addition, pDC dysfunction might lead to immune system dysregulation and excessive and/or prolonged airway inflammation. However, current understanding of how pDC regulate immune function and potentially contribute to asthma pathogenesis remains incomplete.
Targeting citrullination in autoimmunity: insights learned from preclinical mouse models
Published in Expert Opinion on Therapeutic Targets, 2021
Ylke Bruggeman, Fernanda M.C. Sodré, Mijke Buitinga, Chantal Mathieu, Lut Overbergh, Maria J.L. Kracht
SLE is a systemic autoimmune disease that causes damage to multiple organs, including the skin, kidneys and joints. In addition, cardiovascular complications typically arise in patients with SLE as a result of accelerated atherosclerosis and represent an important morbidity cause [86]. Characteristic for SLE is the presence of autoantibodies against nuclear antigens. Accumulation of these nuclear autoantigens results from dying cells and impaired clearance of debris [87]. Deposition of immune complexes (ICs) in tissues stimulate the production of type I Interferons (IFNs) by plasmacytoid dendritic cells (pDCs), driving disease pathogenesis [88]. Many cell death pathways have been implicated as a source of nuclear autoantigens, including apoptosis, necroptosis, pyroptosis, autophagy and NETosis [87,89,90]. Neutrophils, found in kidneys and skin of lupus-patients, showed an increased capacity to release NETs [91]. Lupus NETs also induced pDCs to produce type I IFNs and directly promoted vascular and organ damage [90–92].
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