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Topic Review
Chimeric Antigen Receptor T-Cell Therapy
The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective CAR-T. Chimeric antigen receptor T-cell therapy (CAR-T) is a type of immunotherapy in which a patient’s T cells are collected and genetically engineered to improve their ability to recognize and kill cancer cells. However, several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable.
  • 965
  • 23 Nov 2022
Topic Review
Innate Immune Receptor Stimulation
Immunometabolism is a relatively new field of research that aims at understanding interconnections between the immune system and cellular metabolism. This is now well-documented for innate immune cells of the myeloid lineage such as macrophages and myeloid dendritic cells (DCs) when they engage their differentiation or activation programs. Several studies have shown that stimulation of DCs or macrophages by the binding of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs) leads to increased glycolytic activity and rewiring of central carbon metabolism. These metabolic modulations are essential to support and settle immunological functions by providing energy and immunoregulatory metabolites. As the understanding of molecular mechanisms progressed, significant differences between cell types and species have also been discovered. Pathways leading to the regulation of central carbon metabolism in macrophages and DCs by PRR signaling and consequences on cellular functions are reviewed here.
  • 964
  • 08 Feb 2021
Topic Review
SARS-CoV-2 Dysregulates Neutrophil Degranulation and Reduces Lymphocyte Counts
SARS-CoV-2, the virus that causes COVID-19, has given rise to one of the largest pandemics, affecting millions worldwide. High neutrophil-to-lymphocyte ratios have been identified as an important correlate to poor recovery rates in severe COVID-19 patients. However, the mechanisms underlying this clinical outcome and the reasons for its correlation to poor prognosis are unclear. Furthermore, the mechanisms involved in healthy neutrophils acquiring a SARS-CoV-2-mediated detrimental role are yet to be fully understood. 
  • 964
  • 14 Mar 2022
Topic Review
Epithelial-Mesenchymal Transition Phenotype and Immune System
Carcinoma cells that undergo an epithelial-mesenchymal transition (EMT) and display a predominantly mesenchymal phenotype (hereafter EMT tumor cells) are associated with immune exclusion and immune deviation in the tumor microenvironment (TME). A large body of evidence has shown that EMT tumor cells and immune cells can reciprocally influence each other, with EMT cells promoting immune exclusion and deviation and immune cells promoting, under certain circumstances, the induction of EMT in tumor cells. This cross-talk between EMT tumor cells and immune cells can occur both between EMT tumor cells and cells of either the native or adaptive immune system.
  • 962
  • 22 Apr 2022
Topic Review
Autoimmune and Autoinflammatory Diseases in Chronic Urticaria
Chronic spontaneous urticaria (CSU) is defined as the almost daily occurrence of widespread wheals, angioedema, or both, for more than 6 weeks. It affects 1–2% of the general population, with a higher prevalence in female patients, and is more frequent patients over 20 years of age. More than half of all cases of chronic idiopathic urticaria are thought to occur due to an autoimmune mechanism, specifically the production of autoantibodies against the high-affinity immunoglobulin E (IgE) receptor (FcεRI). The quality of life in these patients is often greatly compromised, also due to the onset of comorbidities represented by other autoimmune diseases, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, celiac disease, and type 1 diabetes, among others.
  • 961
  • 10 Feb 2023
Topic Review
Mast Cells in Unconventional Immunotherapy
Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the reactions of the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodelling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants.
  • 958
  • 22 Apr 2021
Topic Review
Extracellular Cystatin F and CTLs
Cystatin F is a protein inhibitor of cysteine cathepsins that is found intracellularly in the lysosomal/endosomal pathway as well as extracellularly. The extracellular cystatin F can be internalised into bystander cells and can affect cysteine cathepsin activity in recipient cells. In cytotoxic lymphocytes, extracellular cystatin F after internalisation decreases their cytotoxicity by affecting the activation of granzymes, effector molecules of the perforin/granzyme pathway.
  • 956
  • 18 Dec 2020
Topic Review
Immunotherapy with Checkpoint-Inhibitors for HCC
Immune checkpoint inhibitors (ICIs) are beginning to show promise in the clinical management of hepatocellular carcinoma (HCC). Most recently, the anti-programmed death protein-1 (PD-1) agent atezolizumab combined with bevacizumab demonstrated superiority to sorafenib in a Phase 3 randomised clinical trial in the frontline setting. Other ongoing trials of immunotherapy for HCC are exploring different drug combinations, such as a double checkpoint blockade with PD-1 and anti-Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agents or with tyrosine kinase inhibitors. Moreover, ICIs are being tested in the adjuvant and neoadjuvant settings trying to resolve long-time unmet needs in HCC. The results of the ongoing trials will be critical to understanding the extent of the therapeutic role of ICIs in the complex and multifaceted clinical scenario of HCC. Still, there are some critical points which need further attention to clarify the best use of ICIs in HCC patients. For instance, the actual eligibility rate of patients in the real-life scenario, the prompt identification and correct management of immune-mediated adverse events, the identification of biomarkers predicting response or resistance, and strategies to prevent the tumour escape from ICI effect.  Deatail review paper about the current therapeutic scenario of immune checkpoint inhibitors (in particular nivolumab, ipilimumab, atezolizumab, pembrolizumab, durvalumab) for the treatment of hepatocellular carcinoma. The first part of this review is dedicated to the concluded and ongoing clinical trials. The second part deals with the hot topics in the field of immunotherapy borrowing concepts from other cancers and adapting them to the specific scenario of hepatocellular carcinoma.
  • 954
  • 25 Oct 2020
Topic Review
Antiphospholipid Syndrome
Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL). 
  • 954
  • 23 Nov 2020
Topic Review
PD-L1 Expression in Anti-PD-(L)1 Immunotherapy
PD-L1 expression on tumor tissues as assessed by immunohistochemistry has been shown to be an imperfect biomarker that only applies to a limited number of cancers, whereas many patients with PD-L1-negative tumors still respond to anti-PD-(L)1 immunotherapy. Anti-programmed death-1 (PD-1) or anti-programmed death ligand 1 (PD-L1) immunotherapy (anti-PD-(L)1 immunotherapy) has achieved unprecedented clinical efficacy for patients with various types and stages of cancers. PD-L1 expression on tumor tissues has clearly shown the predictive value in many types of cancers, as patient responses to anti-PD-(L)1 immunotherapy are linearly associated with increased levels of PD-L1 expression in many types of cancers. However, positive PD-L1 expression can only partially predict which patients benefit from therapy, as a subset of patients whose tumors lack expression of PD-L1 has also been shown to respond positively to anti-PD-(L)1 immunotherapy.
  • 954
  • 01 Jun 2022
Topic Review
Mitochondrial Dysfunction Involved in the Pathogenesis of ALS
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, the pathogenesis of which is based on alternations in the mitochondria of motor neurons, causing their progressive death. A growing body of evidence shows that more efficient mitophagy could prevent and/or treat this disorder by suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. Mitophagy has been considered one of the main mechanisms responsible for mitochondrial quality control.
  • 954
  • 22 Dec 2022
Topic Review
Tumor Immune Microenvironment in ccRCC
Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. The complex interplay between the immune system and the tumor in ccRCC has important implications for developing new treatment strategies. Immunotherapy, which aims to activate the immune system to recognize and eliminate tumor cells, has shown promise in the treatment of ccRCC, and several immune-based therapies have been approved for clinical use.
  • 954
  • 08 May 2023
Topic Review
Natural Killer Cells and Radiotherapy
Natural Killer (NK) cells are innate immune cells with the unique ability to recognize and kill virus-infected and cancer cells without prior immune sensitization. Radiotherapy is an anti-cancer strategy based on the administration of ionizing radiation, which induces DNA damage and cell death, and that is currently included in more than 50% of all anti-cancer treatments. Radiotherapy was found to directly impair NK cell viability and activity in a dose-dependent manner while modulating tumor cell sensitivity to NK cell-mediated cytotoxicity and the TME, potentially both promoting and impairing NK cell function, depending on dose and tumor heterogeneity, suggesting that combining radiotherapy with strategies to maintain NK cell viability and activity could be beneficial.
  • 953
  • 10 Mar 2021
Topic Review
Microglia in Brain Homeostasis and Neuroinflammation
Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described.
  • 953
  • 23 Aug 2022
Topic Review
Immune Evasion of Mycoplasma bovis
Mycoplasma bovis (M. bovis) causes various chronic inflammatory diseases, including mastitis and bronchopneumonia, in dairy and feed cattle. It has been found to suppress the host immune response during infection, leading to the development of chronic conditions.
  • 950
  • 30 Sep 2021
Topic Review
A Mycobacteriophage-Based Vaccine Platform for SARS-CoV-2
Bacteriophage-based vaccines can generate a protective immune response by safely introducing foreign antigens displayed on, encapsidated within, or genetically encoded by phage. Here authors describe recombinants of mycobacteriophage Bxb1 (a phage infecting Mycobacterium smegmatis) that covalently display and express antigenic peptides of the SARS-CoV-2 Spike protein. Several of these vaccine candidates produced Spike-specific antibodies in immunized mice, but the responses were not neutralizing. This mycobacteriophage-based vaccine platform can likely be improved if delivery of larger antigens is achieved. 
  • 949
  • 06 Dec 2021
Topic Review
Twentieth-Century Paleoproteomics
Proteomics methods can identify amino acid sequences in fossil proteins, thus making it possible to determine the ascription or proximity of a fossil to other species. Before mass spectrometry was used to study fossil proteins, earlier studies used antibodies to recognize their sequences. 
  • 949
  • 16 Aug 2022
Topic Review
Immunological Nudging
The constant activation and deactivation of immunological processes in harmony due to physiological processes is the basis of the immunological homeostasis. Activation may be chemical or physical such as by mechano-transduction. The immunological system in a healthy system can never be deactivated, i.e. silenced without increasing the risk for sudden and complete incapacitation and malfunction. The functionality of this system and it’s often vital reactivity  depends on the immediate “on demand” availability of all major components in the regulatory mechanisms involved.  This is only possible  by constant and subtle, subclinical  activation and deactivation of this system. This is in contrast  to the temporary or occasional nudging of immunological reactions that is intended to provoke specific immune responses.
  • 948
  • 22 Jul 2020
Topic Review
Nutritional Factors in RA
Rheumatoid arthritis (RA) is the most prevalent systemic autoimmune inflammatory disease affecting approximately 1% of the adult population worldwide.
  • 946
  • 29 Apr 2021
Topic Review
IgG N-glycan Signatures as Diagnostic and Prognostic Biomarkers
IgG N-glycans are an emerging source of disease-specific biomarkers. The continued development of glycomic databases and the evolution of glyco-analytic methods have resulted in increased throughput, resolution, and sensitivity. IgG N-glycans promote adaptive immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement activation to combat infection or cancer and promote autoimmunity. In addition to the functional assays, researchers are examining the ability of protein-specific glycosylation to serve as biomarkers of disease. 
  • 942
  • 28 Mar 2023
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