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Topic Review
Manipulating EVs for Therapeutic Applications
Extracellular vesicles (EVs) receive special attention from clinicians due to their assumed usefulness as prognostic markers, immune modulators and physiological delivery tools. The latter application, that supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell. Otherwise, EVs may be passively supplemented with selected cargo, such as miRNAs or siRNA. Furthermore, recent findings imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. In addition, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect.
  • 894
  • 03 Jul 2020
Topic Review
Tumor Necrosis Factor Receptor 2 in Cancer Therapy
Tumor necrosis factor (TNF) receptor 2 (TNFR2) is a type I transmembrane protein and a prototypic member of the TNF receptor superfamily (TNFRSF). TNFR2 belongs to the TRAF (TNF-receptor-associated factor)-interacting subgroup of the TNFRSF and mediates pro-inflammatory effects, but can also stimulate strong anti-inflammatory activities. TNFR2 is  stimulated by the membrane-bound form of TNF (memTNF). TNFR2 expression is typically high in myeloid cells but is also found in certain T- and B-cell subsets and a few non-immune cells such as endothelial cells, glial cells and cardiomyocytes.
  • 894
  • 09 Jun 2022
Topic Review
Tuft Cells
Tuft cells have emerged as the focus of intense interest following the discovery of their chemosensory role in the intestinal tract, and their ability to activate Type 2 immune responses to helminth parasites. Moreover, they populate a wide range of mucosal tissues and are intimately connected to immune and neuronal cells, either directly or through the release of pharmacologically active mediators. They are now recognised to fulfil both homeostatic roles, in metabolism and tissue integrity, as well as acting as the first sensors of parasite infection, immunity to which is lost in their absence. 
  • 891
  • 22 Dec 2023
Topic Review
IRF8
Interferon regulatory factor 8 (IRF8) is a transcription factor of the IRF protein family. IRF8 was originally identified as an essentialfactor for myeloid cell lineage commitment and differentiation. Deletion of Irf8 leads to massive accumulation of CD11b+Gr1+ immature myeloid cells (IMCs), particularly the CD11b+Ly6Chi/+Ly6G− polymorphonuclear myeloid-derived suppressor cell-like cells (PMN-MDSCs). Under pathological conditions such as cancer, Irf8 is silenced by its promoter DNA hypermethylation, resulting in accumulation of PMN-MDSCs and CD11b+ Ly6G+Ly6Clo monocytic MDSCs (M-MDSCs) in mice. IRF8 is often silenced in MDSCs in human cancer patients. MDSCs are heterogeneous populations of immune suppressive cells that suppress T and NK cell activity to promote tumor immune evasion and produce growth factors to exert direct tumor-promoting activity. Emerging experimental data reveals that IRF8 is also expressed in non-hematopoietic cells. Epithelial cell-expressed IRF8 regulates apoptosis and represses Osteopontin (OPN). Human tumor cells may use the IRF8 promoter DNA methylation as a mechanism to repress IRF8 expression to advance cancer through acquiring apoptosis resistance and OPN up-regulation. Elevated OPN engages CD44 to suppress T cell activation and promote tumor cell stemness to advance cancer. IRF8 thus is a transcription factor that regulates both the immune and non-immune components in human health and diseases.
  • 890
  • 31 Aug 2022
Topic Review
FcRn for Biologics' Nasal Delivery
It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium.
  • 889
  • 30 Jun 2021
Topic Review
IFN-α-Conditioned Dendritic Cells
Dendritic cells (DCs) are unique cellular drivers orchestrating adaptive immune response. In the light of the recent success of immune checkpoint inhibitors (ICI) in cancer treatment, DC have recently been reconsidered as critical cellular adjuvants in cancer vaccination. In fact, increasing the presentation of tumor antigens remains one of the major issues for eliciting a strong antitumor immune response. A number of studies have confirmed that type I IFN can efficiently promote the differentiation of peripheral blood monocytes into potent DC (IFN-DC), orientating DC functions towards the priming and expansion of protective antitumor immune responses. IFN-DC can be conveniently exploited for the design of effective strategies of cancer vaccination as a monotherapy or in combination with immune-checkpoint inhibitors or immunomodulatory drugs.
  • 888
  • 09 Nov 2020
Topic Review
Pyroptosis in Inflammasome-Related Disorders
Inflammasomes are multiprotein complexes orchestrating intracellular recognition of endogenous and exogenous stimuli, cellular homeostasis, and cell death. Upon sensing of certain stimuli, inflammasomes typically activate inflammatory caspases that promote the production and release of the proinflammatory cytokines IL-1β, IL-1α, and IL-18 and induce a type of inflammatory cell death known as “pyroptosis”. Pyroptosis is an important form of regulated cell death executed by gasdermin proteins, which is largely different from apoptosis and necrosis. Recently, several signaling pathways driving pyroptotic cell death, including canonical and noncanonical inflammasome activation, as well as caspase-3-dependent pathways, have been reported. While much evidence exists that pyroptosis is involved in the development of several inflammatory diseases, its contribution to inflammasome-related disorders (IRDs) has not been fully clarified. 
  • 886
  • 21 Sep 2022
Topic Review
Radiotherapy Induced Immunogenic Cell Death
The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence sug-gests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as im-mune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI.
  • 885
  • 16 Mar 2021
Topic Review
Advances in Immunotherapy for Hepatitis B
Hepatitis B virus (HBV) is a hepatotropic virus with the potential to cause chronic infection, and it is one of the common causes of liver disease worldwide. Chronic HBV infection leads to liver cirrhosis and, ultimately, hepatocellular carcinoma (HCC). Progress in Hepatitis-B-Specific Immunotherapy is discussed. 
  • 885
  • 17 Oct 2022
Topic Review
Glucocorticoid Receptor and Its Importance in (Patho)physiology
The glucocorticoid receptor (GR) is a very versatile protein that comes in several forms, interacts with many proteins and has multiple functions. Numerous therapies are based on GRs’ actions but the occurrence of side effects and reduced responses to glucocorticoids have motivated scientists to study GRs in great detail. The notion that GRs can perform functions as a monomeric protein, but also as a homodimer has raised questions about the underlying mechanisms, structural aspects of dimerization, influencing factors and biological functions
  • 884
  • 15 Mar 2022
Topic Review
CD83 as Checkpoint Molecule Controlling Resolution of Inflammation
Chronic inflammatory diseases and transplant rejection represent major challenges for modern health care. Thus, identification of immune checkpoints that contribute to resolution of inflammation is key to developing novel therapeutic agents for those conditions. In recent years, the CD83 (cluster of differentiation 83) protein has emerged as an interesting potential candidate for such a “pro-resolution” therapy. This molecule occurs in a membrane-bound and a soluble isoform (mCD83 and sCD83, respectively), both of which are involved in resolution of inflammation. Originally described as a maturation marker on dendritic cells (DCs), mCD83 is also expressed by activated B and T cells as well as regulatory T cells (Tregs) and controls turnover of MHC II molecules in the thymus, and thereby positive selection of CD4+ T cells. Additionally, it serves to confine overshooting (auto-)immune responses. Consequently, animals with a conditional deletion of CD83 in DCs or regulatory T cells suffer from impaired resolution of inflammation. Pro-resolving effects of sCD83 became evident in pre-clinical autoimmune and transplantation models, where application of sCD83 reduced disease symptoms and enhanced allograft survival, respectively.
  • 883
  • 07 Feb 2022
Topic Review
Circulating Cytokines and Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that has no effective treatment. The lack of any specific biomarker that can help in the diagnosis or prognosis of ALS has made the identification of biomarkers an urgent challenge. Multiple panels have shown alterations in levels of numerous cytokines in ALS, supporting the contribution of neuroinflammation to the progressive motor neuron loss. 
  • 882
  • 10 Jan 2022
Topic Review
Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors
The main aim of this work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb.
  • 881
  • 29 Mar 2022
Topic Review
Role of IL-33 Signalling in COVID-19 Inflammatory Status
During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity.
  • 877
  • 08 Dec 2022
Topic Review
HIV Lifecycle
The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. 
  • 876
  • 22 Jan 2024
Topic Review
The Eclectic Nature of Glioma-Infiltrating Macrophages and Microglia
Glioblastomas (GBMs) are complex ecosystems composed of highly multifaceted tumor and myeloid cells capable of responding to different environmental pressures, including therapies. Recent studies have uncovered the diverse phenotypical identities of brain-populating myeloid cells. Differences in the immune proportions and phenotypes within tumors seem to be dictated by molecular features of glioma cells. Furthermore, increasing evidence underscores the significance of interactions between myeloid cells and glioma cells that allow them to evolve in a synergistic fashion to sustain tumor growth.
  • 875
  • 21 Jan 2022
Topic Review
Peripheral Blood-Based Biomarkers
As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients’ immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer. 
  • 873
  • 29 Mar 2022
Topic Review
Cannabinoid Type-2 Receptor Agonist
JWH133, a selective, full functional agonist of the CB2 receptor, has been extensively studied for its potent anti-inflammatory, antiviral, and immunomodulatory properties. JWH133 modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids.
  • 873
  • 25 Oct 2021
Topic Review
Protein Tyrosine Phosphatase Non-Receptor 2 in the Immunity
PTPN2 (protein tyrosine phosphatase non-receptor 2), also called TCPTP (T cell protein tyrosine phosphatase), is a member of the PTP family signaling proteins. Phosphotyrosine-based signaling of this non-transmembrane protein is essential for regulating cell growth, development, differentiation, survival, and migration. 
  • 873
  • 08 Sep 2022
Topic Review
Trypanosoma cruzi Infection; liver involvement
Currently, in Chagas disease, hepatomegaly is cited in most papers published which either study acutely infected patients or experimental models, and we know that the Trypanosoma cruzi can infect multiple cell types in the liver, especially Kupffer cells and dendritic cells. Moreover, liver damage is more pronounced in cases of oral infection, which is mainly found in the Amazon region. However, the importance of liver involvement, including the hepatic immune response, in disease progression does not receive much attention.
  • 872
  • 03 Sep 2021
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