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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.
  • 927
  • 31 Aug 2022
Topic Review
Pathogens Associated with Pre-Eclampsia
Pre-eclampsia, the second most frequent direct source of maternal mortality, is a multisystem gestational disorder characterized by proteinuria and maternal hypertension after the 20th gestational week. Metabolic conditions, immunological changes, and fluctuating hormone levels of the pregnant woman induce a dysbiosis of the oral microbiota and contribute to increase inflammation of periodontal tissues. Periodontal pathogens, as well as inflammatory molecules produced in response to periodontopathogens, could diffuse through the bloodstream inducing a placenta inflammatory response. In addition, periodontopathogens can colonize the vaginal microbiota through the gastrointestinal tract or during oro-genital contact. A cumulative bi-directional relationship between periodontal conditions, pathogens and pre-eclampsia exists.
  • 925
  • 24 Nov 2021
Topic Review
Chasing Uterine Cancer with NK Cell-Based Immunotherapies
Gynecological cancers, including endometrial adenocarcinoma, significantly contribute to cancer incidence and mortality worldwide. The immune system plays a significant role in endometrial cancer pathogenesis. (uterine) NK cells, a component of innate immunity, are among the critical innate immune cells in the uterus crucial in menstruation, embryonic development, and fighting infections. NK cell number and function influence endometrial cancer development and progression. Hence, it becomes crucial to understand the role of local (uterine) NK cells in uterine cancer.
  • 925
  • 20 Feb 2023
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.
  • 922
  • 09 Nov 2020
Topic Review
Tumor Necrosis Factor Receptor 2 in Colorectal Cancer
Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The CRC microenvironment is highly heterogeneous and represents a very complex immunosuppressive platform. Many cytokines and their receptors are vital participants in this immunosuppressive microenvironment. Tumor necrosis factors (TNFs) and TNF receptor 2 (TNFR2) are critical players in the development of CRC. TNFR2 was observed to have increased the immunosuppressive activity of CRC cells via regulatory T cells (T regs) and myeloid-derived suppressor cells (MDSC) in the CRC microenvironment.
  • 922
  • 07 Feb 2023
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.
  • 921
  • 30 Jun 2021
Topic Review
Gut Microbiota and Immunotherapy
Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis.
  • 920
  • 26 Aug 2022
Topic Review
Protein-Based Adjuvants
 New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. Notably, despite structural differences, all protein-based adjuvants (PBAs) show significant immunostimulatory properties, eliciting B-cell- and T-cell-mediated immune responses to administered antigens, providing advantages over many adopted adjuvant approaches. Furthermore, PBAs are natural biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity and interact with innate immune receptors, enhancing their endocytosis and modulating subsequent adaptive immune responses. This entry proposes that PBAs can contribute to the development of vaccines against complex pathogens, including intracellular pathogens such as Mycobacterium tuberculosis, those with complex life cycles such as Plasmodium falciparum, those that induce host immune dysfunction such as HIV, those that target immunocompromised individuals such as fungi, those with a latent disease phase such as Herpes, those that are antigenically variable such as SARS-CoV-2 and those that undergo continuous evolution, to reduce the likelihood of outbreaks.
  • 919
  • 09 Dec 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.
  • 918
  • 16 Mar 2021
Topic Review
Pregnancy and Vaccination during COVID-19 Pandemic
Pregnancy, alone, being associated with a state of immune alterations, exposes the maternal immune system to many challenges. Pregnant women, being a highly vulnerable group, need to be administered vaccines as early as possible; however, there is a lot of vaccine hesitancy among the population regarding immunization of pregnant women, who are avoided in the initial phases of most clinical trials. A look at available studies on the mechanisms of immune response in pregnant women and further, the reports of vaccine efficacy and outcomes among pregnant women against COVID-19 and EVD would definitely yield many insights that could be useful in the surveillance and planning of vaccination strategies for pregnant women against impending pathogenic RNA viruses.
  • 918
  • 27 Jul 2022
Topic Review
The Link between Implant Failures and Titanium Allergy
Cases of probable titanium allergy included those with true titanium allergies and those with a potentially different cause. However, the differentiation of these cases is difficult. Since no definitive method has been established for diagnosing titanium allergy, a comprehensive diagnosis based on the clinical course and clinical examination using a patch test/lymphocyte transformation test (LTT)/memory lymphocyte immunostimulation assay (MELISA) is necessary. Implant treatment should be performed with caution in patients with any preoperative allergies.
  • 918
  • 20 Nov 2023
Topic Review
Lot-to-Lot Variance in Immunoassays
Immunoassays, which have gained popularity in clinical practice and modern biomedical research, play an increasingly important role in quantifying various analytes in biological samples. Despite their high sensitivity and specificity, as well as their ability to analyze multiple samples in a single run, immunoassays are plagued by the problem of lot-to-lot variance (LTLV). LTLV negatively affects assay accuracy, precision, and specificity, leading to considerable uncertainty in reported results. Therefore, maintaining consistency in technical performance over time presents a challenge in reproducing immunoassays.
  • 916
  • 15 Jun 2023
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.
  • 913
  • 09 Jun 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
  • 912
  • 15 Mar 2022
Topic Review
SARS-CoV-2 Pandemic in Our Time
Coronavirus disease-19 (a.k.a. COVID-19) is a new disease caused by a coronavirus that is still under investigation concerning how it spreads. Development and deployment of biosensors for the rapid detection of the 2019 novel severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2) are of utmost importance and urgency during this recent outbreak of coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection, which spread rapidly around the world. 
  • 912
  • 08 Apr 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. 
  • 909
  • 10 Jan 2022
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. 
  • 909
  • 17 Oct 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.
  • 909
  • 25 Oct 2021
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.
  • 903
  • 03 Jul 2020
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.
  • 897
  • 29 Mar 2022
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