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Topic Review
Immune Checkpoint Inhibitors
There are several forms of Immune checkpoint inhibitors (ICIs) targeting at several checkpoint proteins or receptors including programmed cell death 1 (PD-1), PD-1 ligand (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), B and T cell lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and T cell immunoglobulin and mucin domain 3 (TIM-3) [5,6,7,8,9]. ICIs, specifically PD-1, PDL-1 and CTLA-4 inhibitors have been approved for the treatment of a variety of solid tumors, initially beginning with melanoma in 2011. Both PD-1 and CTLA-4 are negative costimulatory molecules that when inhibited enhance T cell activation and the eventual killing of tumor cells [10].ICIs can be used in patients with chemotherapy-resistant tumors through tissue agnostic approval for MSI-H and high mutational burden tumors [14]. ICIs have shown that they are not only efficacious but have superior safety profile as well [15]. Most of the ICIs are well tolerated, however, they have distinct side effects compared to traditional cytotoxic chemotherapies [16,17].
  • 1.2K
  • 27 Oct 2020
Topic Review
Adoptive Immunotherapy beyond CAR T-Cells
The aging of the world population leads to a constant increase of cancer-related morbidity and mortality. Treatment of late-stage tumors has become a significant burden on the healthcare system globally. Adoptive cell immunotherapy is supposed to prolong life with cancer and ideally cure cancer after a single infusion of the cell product. Arguably, the most impressive clinical therapy in this field is based on chimeric antigen receptor (CAR) T-cells capable of curing up to 25–50% of previously incurable patients with B-cell malignancies. Diverse cell therapies are already efficiently used in clinics for cancer treatment (such as tumor infiltrating lymphocytes, transgenic αβ T-cells) and several novel promising cell therapies are in development (such as CAR M-cells, transgenic γδ T-cells, CAR NK-cells). Here, we summarize the recent literature data with the focus on T-cell receptor-based therapies and overview the most advanced systems for manufacturing of clinical grade cell products. 
  • 1.2K
  • 22 Dec 2021
Topic Review
Rheumatic Manifestations for ICIs
Immune checkpoint inhibitors (ICI) are monoclonal antibodies that activate the immune system aiming at enhancing antitumor immunity.  Their clinical efficacy is well documented but the side effects associated with their use are still under investigation.  These drugs cause several immune related adverse events (ir-AE) some of which stand within the field of Rheumatology.  Herein, we performed a literature review in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICI.  The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis.  Non musculoskeletal rheumatic manifestations are less frequent with the most prominent being sicca, vasculitides and sarcoidosis.  Cases of systemic lupus erythematosus or scleroderma are extremely rare.  The majority of musculoskeletal ir-AE are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation.  In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed.  Oncologists should periodically screen patients receiving ICI for new onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.
  • 1.2K
  • 28 Oct 2020
Topic Review
Role of Selenium in Viral Infections
Viral infections have afflicted human health and despite great advancements in scientific knowledge and technologies, continue to affect our society today. The current coronavirus (COVID-19) pandemic has put a spotlight on the need to review the evidence on the impact of nutritional strategies to maintain a healthy immune system, particularly in instances where there are limited therapeutic treatments. Selenium, an essential trace element in humans, has a long history of lowering the occurrence and severity of viral infections. Much of the benefits derived from selenium are due to its incorporation into selenocysteine, an important component of proteins known as selenoproteins. Viral infections are associated with an increase in reactive oxygen species and may result in oxidative stress. Studies suggest that selenium deficiency alters immune response and viral infection by increasing oxidative stress and the rate of mutations in the viral genome, leading to an increase in pathogenicity and damage to the host. 
  • 1.2K
  • 19 Jan 2022
Topic Review
Yeast β-Glucan with Immune-Modulatory Properties
β-glucans are a large class of complex polysaccharides with bioactive properties, including immune modulation. Natural sources of these compounds include yeast, oats, barley, mushrooms, and algae. Yeast is abundant in various processes, including fermentation, and they are often discarded as waste products. The production of biomolecules from waste resources is a growing trend worldwide with novel waste resources being constantly identified. Yeast-derived β-glucans may assist the host’s defence against infections by influencing neutrophil and macrophage inflammatory and antibacterial activities. β-glucans were long regarded as an essential anti-cancer therapy and were licensed in Japan as immune-adjuvant therapy for cancer in 1980 and new mechanisms of action of these molecules are constantly emerging.
  • 1.2K
  • 01 Jun 2022
Topic Review
Magnetic Nanostructures for Cancer Immunotherapy
Magnetic nanoparticles (MNPs) represent an attractive class of nanomaterials due to their unique physical and chemical features that allow them to respond specifically to magnetic fields. Among the magnetic class of materials, iron oxide-based nanoparticles are the only inorganic nanomaterials that have been approved by the Food and Drug Administration (FDA) for medical applications. Magnetic nanomaterials are particularly appealing for cancer immunotherapy due to their unique features, which include (i) the traceability of their signal by magnetic resonance imaging (MRI) or by magnetic particle imaging (MPI) techniques ; (ii) their exploitation as carriers to promote the accumulation and the efficient delivery of biotherapeutic compounds, such as genes and peptides, into a specific target cell or tissue; (iii) their ability to mediate the elimination of cancer cells through the production of a local thermo-ablative effect when exposed to an external alternating magnetic field, referred to as magnetic hyperthermia therapy (MHT); and (iv) their intrinsic immunomodulatory properties that can be harnessed to further promote or modulate the immune function.
  • 1.2K
  • 07 Jul 2021
Topic Review
The Viral Agents of BRDC
Bovine respiratory disease complex (BRDC) is a multifactorial disease of cattle which presents as bacterial and viral pneumonia. The causative agents of BRDC work in synergy to suppress the host immune response and increase the colonisation of the lower respiratory tracts by pathogenic bacteria. Environmental stress and/or viral infection predispose cattle to secondary bacterial infections via suppression of key innate and adaptive immune mechanisms. This allows bacteria to descend the respiratory tract unchallenged. BRDC is the costliest disease among feedlot cattle, and whilst vaccines exist for individual pathogens, there is still a lack of evidence for the efficacy of these vaccines and uncertainty surrounding the optimum timing of delivery. 
  • 1.2K
  • 14 Apr 2021
Topic Review
Innate Lymphoid Cells in Pancreatic Disease
Innate lymphoid cells (ILCs) represent a heterogeneous population of non-B/non-T lymphocytes whose discovery has greatly expanded researchers understanding over the past 10 years. ILCs are defined mainly by three unique features: (1) their lymphoid morphology; (2) their lack of genetically rearranged antigen receptors; and (3) their deficiency of cell-surface markers expressed in other immune cell types, such as myeloid cells and dendritic cells. In recent years, emerging evidence has identified the existence of ILCs in the pancreas, and all ILC subsets have been identified. ILCs resident in the pancreas, as well as in other tissues, may play an important role in the occurrence and progression of pancreatic diseases and will therefore be expected to be applied in the prevention and treatment of these diseases.
  • 1.2K
  • 22 Apr 2022
Topic Review
Ezrin, VASO-Active Intestinal Peptide and COVID-19
SARS-CoV-2 infection inhibits interferon expression, while hyper-activating innate-immune signalling and expression of pro-inflammatory cytokines. SARS-CoV-2 proteins: Spike, M and nsp6, nsp12 and nsp13 inhibit IFR3-mediated Type-1-interferon defence, but hyper-activate intracellular signalling, which leads to dysfunctional expression of pro-inflammatory cytokines, particularly IL-1β IL-6, IL-8, and TNFα. Ezrin, a sub-membrane adaptor-protein, organises multi-protein-complexes such as ezrin+NHERF1+NHE+CFTR, which control the density and location of ACE2 receptor expression on the luminal surface of airway-epithelial-cells, as well as determining susceptibility to SARS-CoV-2 infection. This protein complex is vital for lung-surfactant production for efficient gas-exchange. Ezrin also forms multi-protein-complexes that regulate signalling kinases; Ras, PKC, PI3K, and PKA. m-RAGE is a pattern-recognition-receptor of the innate immune system that is triggered by AGEs, which are chemically modified proteins common in the elderly and obese. Vasoactive Intestinal Peptide (VIP) is a 28-amino acid peptide released by intrinsic neurons in the human airways. 
  • 1.2K
  • 22 Apr 2022
Topic Review
Metformin Protects Livers against NASH-related-HCC
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models.
  • 1.2K
  • 12 Oct 2021
Topic Review
HIV mRNA Vaccine Platforms
The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.
  • 1.2K
  • 25 Jun 2021
Topic Review
Adaptive Immune-Response to Tick-Borne Hemoparasites
Interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, involved in the late and long-lasting protective immune response. 
  • 1.2K
  • 02 Dec 2020
Topic Review
Phenotypical and Functional Polymorphism of Liver Resident Macrophages
Liver diseases are one of the main causes of mortality. In this regard, the development of new ways of reparative processes stimulation is relevant. Macrophages play a leading role in the regulation of liver homeostasis in physiological conditions and in pathology. In this regard, the development of new liver treatment methods is impossible without taking into account this cell population. Resident macrophages of the liver, Kupffer cells, represent a unique cell population, first of all, due to their development. Most of the liver macrophages belong to the self-sustaining macrophage cell population, whose origin is not bone marrow. In addition, Kupffer cells are involved in such processes as regulation of hepatocyte proliferation and apoptosis, remodeling of the intercellular matrix, lipid metabolism, protective function, etc. Such a broad spectrum of liver macrophage functions indicates their high functional plasticity. The Recent data on the development, phenotypic and functional plasticity, and participation in the reparative processes of liver macrophages: resident macrophages (Kupffer cells) and bone marrow-derived macrophages were summarized.
  • 1.2K
  • 29 Jan 2022
Topic Review
The Formyl Peptide Receptors
The formyl peptide receptors, abbreviated as formyl peptide receptors (FPRs) in humans, are pattern recognition receptors (PRRs) with central roles in host defense and inflammation.
  • 1.2K
  • 15 Dec 2022
Topic Review
NF-κB Signaling Pathways
Drosophila are a well-suited model to unravel the fundamental mechanisms that constitute the innate immune response. NF-κB was originally identified as a DNA-binding activity protein in activated B cells.
  • 1.2K
  • 11 Oct 2022
Topic Review
Neutrophils and Angiogenesis in Cancer
Tumor angiogenesis is one of the most critical steps in the progression of cancer. Owing to its fundamental role in tumor growth and metastasis, tumor angiogenesis is accepted to be a limiting factor and considered a powerful therapeutic target. Neutrophils contribute to the tumor progression via multiple mechanisms, ranging from the direct support of tumor cell survival to the immunosuppression. A strong body of evidence suggests that neutrophils also play a prominent role in tumor angiogenesis.
  • 1.2K
  • 29 Mar 2022
Topic Review
Peptide-Based Vaccines for Breast Cancer
Breast cancer (BC) is the main type of cancer in women and the second most frequent cancer worldwide. The conventional treatment includes surgery, chemotherapy, hormonal therapy, and immunotherapy. This immunotherapy is based on administering monoclonal therapeutic antibodies (passive) or vaccines (active) with therapeutic purposes. Tumor antigens are classified as tumor-associated antigens (TAAs) and tumor-specific antigens (TSA). New TAAs were proposed for the formulation of peptide-based vaccines, including MUC-1 (mucin-1), FRα (folate receptor alpha), members of the MAGE A family (melanoma-associated antigen), and EGFR (epidermal growth factor receptor).
  • 1.2K
  • 26 Aug 2022
Topic Review
The Adaptor Protein p66Shc
p66Shc is an adaptor protein with anti-mitogenic, anti-chemotactic, pro-apoptotic and pro-oxidant activities.  Neoplastic B cells from chronic lymphocytic leukemia (CLL) patients  have a profound deficiency in the expression of p66Shc which results in leukemic cell resistance to apoptosis and in an altered balance between homing and egress receptors that control B cell homing to and residency into the pro-survival lymphoid niche. Ablation of the gene encoding p66Shc in the Eμ-TCL1 mouse model of human CLL worsens disease presentation  by promoting leukemic cell invasiveness, providing in vivo evidence of the pathogenic role of the p66Shc defect in CLL pathogenesis. Here we briefly summarize the functions of p66Shc in lymphocytes, focalizing on the mechanisms exploited by p66Shc to control B cell trafficking and the abnormalities in this process caused by p66Shc deficiency in CLL. 
  • 1.2K
  • 12 Nov 2020
Topic Review
Joint-Preserving Surgery
The concept of “joint-preservation” was introduced by Hanyu et al. in 1997. They started joint-preserving surgery to preserve the function of the MTP joints as they recognized its function as important for gait even in patients with RA.
  • 1.2K
  • 23 Apr 2021
Topic Review
Evolution of TFs and Enhancers
Adaptive immunity relies on the V(D)J DNA recombination of immunoglobulin (Ig) and T cell receptor (TCR) genes, which enables the recognition of highly diverse antigens and the elicitation of antigen-specific immune responses. This process is mediated by recombination-activating gene (Rag) 1 and Rag2 (Rag1/2), whose expression is strictly controlled in a cell type-specific manner; the expression of Rag1/2 genes represents a hallmark of lymphoid lineage commitment. Although Rag genes are known to be evolutionally conserved among jawed vertebrates, how Rag genes are regulated by lineage-specific transcription factors (TFs) and how their regulatory system evolved among vertebrates have not been fully elucidated. Here, we review the current body of knowledge concerning the cis-regulatory elements (CREs) of Rag genes and the evolution of the basic helix-loop-helix TF E protein regulating Rag gene CREs, as well as the evolution of the antagonist of this protein, the Id protein. This may help to understand how the adaptive immune system develops along with the evolution of responsible TFs and enhancers. 
  • 1.2K
  • 09 Jun 2021
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