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Topic Review
Immunotherapy during the Immediate Perioperative Period
Tumor excision is a necessary life-saving procedure in most solid cancers. However, surgery and the days before and following it, known as the immediate perioperative period (IPP), entail numerous prometastatic processes, including the suppression of antimetastatic immunity and direct stimulation of minimal residual disease (MRD). Thus, the IPP is pivotal in determining long-term cancer outcomes, presenting a short window of opportunity to circumvent perioperative risk factors by employing several therapeutic approaches, including immunotherapy. Nevertheless, immunotherapy is rarely examined or implemented during this short timeframe, due to both established and hypothetical contraindications to surgery. This entry summarizes existing and potential immuno-theraputic approaches to exploit the immediate perioperative period to prevent future metastatic disease.
  • 763
  • 23 Aug 2023
Topic Review
Bone Marrow as Central Immune System
Bone marrow is known as the site of hematopoiesis. What is not being described in textbooks of immunology is the fact that bone marrow is not only a generative, but also an antigen-responsive, immune organ. It is also a major storage site for antigen-specific memory B and T cells.
  • 761
  • 08 Aug 2023
Topic Review
Natural Killer Cells in Cancer: Mechanisms of Dysfunction
Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. Consequently, adoptive transfer of autologous or allogeneic NK cells represents a novel opportunity in cancer treatment that is under clinical investigation. However, cancer renders NK cells dysfunctional, thus restraining the efficacy of cell-based therapies.
  • 760
  • 21 Jun 2023
Topic Review
HIV Vaccine Development
An HIV vaccine can be either a preventive vaccine or a therapeutic vaccine, which means it can either protect individuals from being infected with HIV or treat HIV-infected individuals. And it can either induce an immune response against HIV (active vaccination approach) or consist of preformed antibodies against HIV (passive vaccination approach). There is currently no licensed HIV vaccine on the market, but multiple research projects are trying to find an effective vaccine. Evidence observed from humans shows that a vaccine may be possible: Some, but certainly not all, HIV-infected individuals naturally produce broadly neutralizing antibodies which keep the virus suppressed, and these people remain asymptomatic for decades. Potential broadly neutralizing antibodies have been cloned in the laboratory (monoclonal antibodies) and are being tested in passive vaccination clinical trials. Many trials have shown no efficacy, but one HIV vaccine regimen, RV 144, has been shown to prevent HIV in some individuals in Thailand. The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 35 million people since 1981. In 2002, AIDS became the primary cause of death due to an infectious agent in Africa. Alternative medical treatments to a vaccine exist. For the treatment of HIV-infected individuals, highly active antiretroviral therapy (HAART) medication has been demonstrated to provide many benefits to HIV-infected individuals, including improved health, increased lifespan, control of viremia, and prevention of transmission to babies and partners. HAART must be taken lifelong without interruption to be effective, and cannot cure HIV. Options for the prevention of HIV infection in HIV-uninfected individuals include safer sex (for example condom use), antiretroviral strategies (pre-exposure prophylaxis and post-exposure prophylaxis) and medical male circumcision. Vaccination has proved a powerful public health tool in vanquishing other diseases, and an HIV vaccine is generally considered as the most likely, and perhaps the only way by which the HIV pandemic can be halted. However, HIV remains a challenging target for a vaccine.
  • 758
  • 27 Oct 2022
Topic Review
Inflammasome-Mediated Cytokines
Liver cancer is one of the most lethal malignancies and is commonly diagnosed as hepatocellular carcinoma (HCC), a tumor type that affects about 90% of patients. Non-alcoholic steatohepatitis (NASH) and obesity are both risk factors for this disease. HCC initiation and progression are deeply linked with changes in the hepatic microenvironment, with cytokines playing key roles. The understanding of the pathogenic pathways that connect these disorders to liver cancer remains poor.
  • 756
  • 07 Feb 2023
Topic Review
Dendritic Cells as Multifaceted Orchestrators of Immune Responses
Immune-mediated inflammatory diseases (IMIDs) are a group of autoimmune and chronic inflammatory disorders with constantly increasing prevalence in the modern world. The vast majority of IMIDs develop as a consequence of complex mechanisms dependent on genetic, epigenetic, molecular, cellular, and environmental elements, that lead to defects in immune regulatory guardians of tolerance, such as dendritic (DCs) cells.
  • 754
  • 24 Nov 2022
Topic Review
Endosomal TLR Agonists Improving NK Cell Function
Toll-like receptors (TLRs) are the most well-defined pattern recognition receptors (PRR) of several cell types recognizing pathogens and triggering innate immunity. TLRs are also expressed on tumor cells and tumor microenvironment (TME) cells, including natural killer (NK) cells. Cell surface TLRs primarily recognize extracellular ligands from bacteria and fungi, while endosomal TLRs recognize microbial DNA or RNA. TLR engagement activates intracellular pathways leading to the activation of transcription factors regulating gene expression of several inflammatory molecules. Endosomal TLR agonists may be considered as new immunotherapeutic adjuvants for dendritic cell (DC) vaccines able to improve anti-tumor immunity and cancer patient outcomes.
  • 753
  • 09 Mar 2023
Topic Review
B-Cell Activating Factor in IBD
B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily. BAFF is predominantly produced by myeloid cells (monocytes, macrophages, dendritic cells and neutrophils), and its main role is regulation of mature B cell survival and differentiation into antibody-producing plasma cells. Overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus (SLE), where BAFF-inhibitor belimumab was approved for treatment.
  • 749
  • 27 Jan 2022
Topic Review
NKG2A Immune Checkpoint in Vδ2 T Cells
Targeting NKG2A immune checkpoint by gene knockout or blocking antibodies improves the cytotoxicity of Vδ2 T cells, a specific subset of human unconventional γδ T lymphocytes. Thus, a suitable selection of NKG2A+ or NKG2A− Vδ2 T cells for expansion or engineering could help to narrow the Vδ2 T cell population according to the expression of HLA-E on tumor cells. With this emerging knowledge, approaches to target NKG2A in Vδ2 T cells might be a promising step forward to boosting Vδ2 T cell-based cancer immunotherapies.
  • 748
  • 02 Mar 2023
Topic Review
Epigenetic Modifiers in T Cells
Immunotherapy has brought new hope for cancer patients. There is still a need to address major challenges including heterogeneity in response among patients, the reoccurrence of the disease, and iRAEs (immune-related adverse effects). The first critical step towards solving these issues is understanding the epigenomic events that play a significant role in the regulation of specific biomolecules in the context of the immune population present in the tumor immune microenvironment (TIME) during various treatments and responses.
  • 746
  • 08 Feb 2023
Topic Review
Molecular Basis of Ferroptosis
Ferroptosis is a recently recognized iron-dependent form of non-apoptotic regulated cell death (RCD) characterized by lipid peroxide accumulation to lethal levels. Cancer cells, which show an increased iron dependency to enable rapid growth, seem vulnerable to ferroptosis. There is also increasing evidence that ferroptosis might be immunogenic and therefore could synergize with immunotherapies. Hepatocellular carcinoma (HCC) is the most common primary liver tumor with a low survival rate due to frequent recurrence and limited efficacy of conventional chemotherapies, illustrating the urgent need for novel drug approaches or combinatorial strategies. Immunotherapy is a new treatment approach for advanced HCC patients.
  • 745
  • 03 Mar 2022
Topic Review
Targeted Microbial Therapies for Food Allergy
Food allergies have been rising in prevalence in recent decades and are also the most common cause of anaphylaxis in children. Food allergies impose significant burdens on patients and families due to the need for specialized diets and constant monitoring for allergens in food, increased healthcare usage, and anxiety related to developing an anaphylactic reaction.
  • 744
  • 19 Dec 2022
Topic Review
Autoimmune Arthritis and Nephritis
Autoimmune arthritis and nephritis are intractable conditions and there are many unresolved issues. This topic solicits the latest findings and evidence from a wide range of fields. Reviews, basic experiments and clinical studies are welcome.
  • 743
  • 26 Sep 2020
Topic Review
Rheumatoid Arthritis Treatment
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that deteriorates quality and function of the synovium membrane, resulting in chronic inflammation, pain and progressive cartilage and bone destruction. The mechanism of RA pathogenesis is associated with dysregulation of innate and adaptive immunity.
  • 743
  • 06 Dec 2021
Topic Review
Myeloid-Derived Suppressor Cells in Cancer and COVID-19
Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS.
  • 742
  • 02 Feb 2023
Topic Review
Neurocognitive Symptoms Due to Respiratory infections
Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations.
  • 741
  • 18 Jan 2022
Topic Review
IL-17-Member Family
T-helper 17 (Th17) cells represent a subpopulation of CD4+ T lymphocytes that play an essential role in defense against pathogens. Th17 cells are distinguished from Th1 and Th2 cells by their ability to produce members of the interleukin-17 (IL-17) family, namely IL-17A and IL-17F. IL-17 in turn induces several target cells to synthesize and release cytokines, chemokines, and metalloproteinases, thereby amplifying the inflammatory cascade. Th17 cells reside predominantly in the lamina propria of the mucosa.
  • 739
  • 03 Jan 2023
Topic Review
Metabolism in Chimeric Antigen Receptor T Cells
The manufacture of efficacious chimeric antigen receptor (CAR) T cells represents a major challenge in cellular therapy. An important aspect of their quality concerns energy production and consumption, known as metabolism. T cells tend to adopt diverse metabolic profiles depending on their differentiation state and their stimulation level. It is therefore expected that the introduction of a synthetic molecule such as CAR, activating endogenous signaling pathways, will affect metabolism. In addition, upon patient treatment, the tumor microenvironment might influence the CAR T cell metabolism by compromising the energy resources. The access to novel technology with higher throughput and reduced cost has led to an increased interest in studying metabolism. Indeed, methods to quantify glycolysis and mitochondrial respiration have been available for decades but were rarely applied in the context of CAR T cell therapy before the release of the Seahorse XF apparatus. 
  • 738
  • 13 May 2022
Topic Review
Galectin-9 and Osteopontin Reflect COVID-19
Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN.
  • 737
  • 24 May 2021
Topic Review
Monoclonal Antibodies
The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected.
  • 732
  • 19 Feb 2024
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