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Topic Review
The Tumor-Intrinsic NLRP3-HSP70 Signaling Axis in Immune Evasion
The tumor-intrinsic NLRP3 inflammasome is a newly recognized player in the regulation of tumor-directed immune responses and promises to provide fresh insight into how tumors respond to immunotherapy. 
  • 715
  • 29 Mar 2022
Topic Review
Immune Infiltrates in Breast Cancer
In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. 
  • 714
  • 02 Feb 2021
Topic Review
Interactions between Pathogenic Virus and Vertebrate Host
Basic models of the interactions between a pathogenic virus and vertebrate animal host are described. The interactions at the population level are described by a predatory-prey model, a common approach in the ecological sciences, and depend on births and deaths within each population. This ecological perspective is complemented by models at the genetical level, which includes the dynamics of gene frequencies and the mechanisms of evolution. There are varieties of viruses that depend on the cells of a vertebrate host. These virus types may be classified according to their genetic material, such as whether their genetic package is composed of the nucleic acid DNA or RNA. 
  • 714
  • 14 Nov 2022
Topic Review
Circulating Leukocytes in People Mildly Infected by SARS-CoV-2
Mild SARS-CoV-2 infections (n = 22), compared to those that had recovered from other mild respiratory infections (n = 11). Individuals who had experienced mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1–3 months after symptom onset, and changes in phenotype and function of circulating T-cells that were not apparent in individuals 6–9 months post-symptom onset. Markers of monocyte activation, and expression of adherence and chemokine receptors indicative of altered migratory capacity, were also higher at 1–3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6–9 months post-infection. Perhaps most surprisingly, significantly more T-cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS-CoV-2, infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS-CoV-2 infections. 
  • 710
  • 07 Dec 2021
Topic Review
Functional Ambivalence of Dendritic Cells
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents. Tolerogenic dendritic cells (tDCs) induce immune tolerance by activating CD4+CD25+Foxp3+ regulatory T (Treg) cells and/or by producing cytokines that inhibit T cell activation. These findings suggest that tDCs may be an effective treatment for autoimmune diseases, inflammatory diseases, and infertility.
  • 709
  • 28 Apr 2021
Topic Review
Immunomodulation, Bioavailability and Safety of Bacteriocins
Bacteriocins can help in the treatment and prevention of infectious diseases. Moreover, bacteriocins can be obtained in prokaryotic organisms, and contribute s to their widespread use. While the use of bacteriocins is currently limited to the food industry (for example, nisin is used as a preservative, E234), a large number of studies on their microbicidal properties suggest that their use in medicine may increase in the foreseeable future. However, for the successful use of bacteriocins in medicine, it is necessary to understand their effect on the immune system, especially in cases where immunity is weakened due to infectious processes, oncological, allergic, or autoimmune diseases. Studies on the immuno-modulatory activity of bacteriocins in animal models and human cells have revealed their ability to induce both pro-inflammatory and anti-inflammatory factors involved in the implementation of innate immunity. The influence of bacteriocins on acquired immunity is revealed by an increase in the number of T-lymphocytes with a simultaneous decrease in B-lymphocyte levels, which makes them attractive substances for reducing inflammation. The widespread use of bacteriocins in the food industry, their low toxicity, and their broad and narrow specificity are reasons for researchers to pay attention to their immunomodulatory properties and explore their medical applications. Inflammation regulation by bacteriocins can be used in the treatment of various pathologies.
  • 708
  • 24 Jul 2023
Topic Review
Effects of Dental Calculus-Induced Cytokines on Osteoclastogenesis
Dental calculus (DC) is a common deposit in periodontitis patients. DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokines, such as IL-1β and IL-18, via the NLRP3 inflammasome in macrophages.
  • 705
  • 21 Dec 2021
Topic Review
The Neonatal Immune System
The immune system is a complex network of cells and signals which regulate the host’s response to self and foreign antigens. This delicate system requires substantial regulation to prevent severe damage to the host but is also balanced against the potential damage that could be inflicted if a response is not generated. Thus, responses are primarily dependent on the needs of the hosts and the nature of the signal. In the case of immune stimulation by pathogens, the primary goal of the immune system is to mediate clearance of the pathogen while minimizing damage inflicted to the host by the immune response itself. The adult immune system, which is better studied and understood than is the neonatal one, efficiently generates pro-inflammatory responses which mediate the efficient control of most pathogens. The neonatal immune system, however, is evolved to respond to the unique challenges of the rapid transition from the near-sterile womb to the microbe-rich world beyond. This suddenly introduces millions of new antigens for potential immune recognition and response, a seemingly impossible feat. Therefore, during this transition from near-sterile-fetal to microbe-rich neonatal environment, the immune system is evolved to respond to novel antigens primarily with anti-inflammatory TH2 responses to prevent unnecessary inflammation which can severely harm the infant.
  • 705
  • 29 Jun 2023
Topic Review
Multistability in Macrophage Activation Pathways
Macrophages are innate immune cells with a dynamic range of reversible activation states including the classical pro-inflammatory (M1) and alternative anti-inflammatory (M2) states. Common regulatory motifs reported for macrophage transitions, such as positive or double-negative feedback loops, exhibit a switchlike behavior, suggesting the bistability of the system.  There are evidence for multistability (including bistability) in macrophage activation pathways at four molecular levels.
  • 704
  • 22 Feb 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.
  • 704
  • 09 Mar 2023
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.
  • 704
  • 02 Mar 2023
Topic Review
Immune Response to Tuberculosis Infection: A Structural Overview
Tuberculosis (TB) is the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is an urgent global public health priority. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development. The contribution of Structural Vaccinology (SV) to the development of safer and effective antigens is discussed herein.
  • 703
  • 07 Feb 2023
Topic Review
Molecular Mechanisms in Fibrotic Evolution during Autoimmune Diseases
Autoimmunity is a chronic process resulting in inflammation, tissue damage, and subsequent tissue remodelling and organ fibrosis. In contrast to acute inflammatory reactions, pathogenic fibrosis typically results from the chronic inflammatory reactions characterizing autoimmune diseases. Despite having obvious aetiological and clinical outcome distinctions, most chronic autoimmune fibrotic disorders have in common a persistent and sustained production of growth factors, proteolytic enzymes, angiogenic factors, and fibrogenic cytokines, which together stimulate the deposition of connective tissue elements or epithelial to mesenchymal transformation (EMT) that progressively remodels and destroys normal tissue architecture leading to organ failure. 
  • 701
  • 25 May 2023
Topic Review
Natural Killer Cells in Myelodysplastic Syndrome
Myelodysplastic syndrome (MDS) treatment remains a big challenge due to the heterogeneous nature of the disease and its ability to progress to acute myeloid leukemia (AML). The only curative option is allogeneic hematopoietic stem cell transplantation (HSCT), but most patients are unfit for this procedure and are left with only palliative treatment options, causing a big unmet need in the context of this disease. Natural killer (NK) cells are attractive candidates for MDS immunotherapy due to their ability to target myeloid leukemic cells without prior sensitization.
  • 696
  • 28 Feb 2023
Topic Review
Toll-Like Receptors in Brief
Toll-like receptors (TLRs) are pivotal components of the innate immune system, acting as vigilant sentinels that detect microbial threats and orchestrate immune responses. This research navigates the intricate world of TLRs, commencing with their discovery, evolutionary significance, and structural attributes. 
  • 695
  • 08 Oct 2023
Topic Review
ATF4 Role during HIV-1 Replication
Activating transcription factor 4 (ATF4) is a transcription factor known to regulate genes associated with the sensing of cellular stress such as amino acid deprival, protein misfolding, growth arrest, and cell death. Despite its key role at the crossroads of immune and stress responses, the precise impact of ATF4 during viral infections remains unclear. Thus, ATF4 has a dual role in promoting cell survival or cell death, but also in limiting infection or participating in viral replication.
  • 695
  • 18 Mar 2024
Topic Review
Vaccines in Gastrointestinal Malignancies
Gastrointestinal (GI) malignancies are some of the most common malignancies and include colorectal, gastric, esophageal, hepatocellular, and pancreatic carcinomas. Overall five-year survival rates for many of these malignancies are low, with many patients presenting with advanced disease. Thus, it is important to continue to investigate and create novel therapeutic interventions to treat these malignancies.
  • 694
  • 30 Jun 2021
Topic Review
Butyrophilins
The efficacy of current immunotherapies remains limited in many solid epithelial malignancies. Recent investigations into the biology of butyrophilin (BTN) and butyrophilin-like (BTNL) molecules, however, suggest these molecules are potent immunosuppressors of antigen-specific protective T cell activity in tumor beds. BTN and BTNL molecules also associate with each other dynamically on cellular surfaces in specific contexts, which modulates their biology. 
  • 694
  • 24 May 2023
Topic Review
Innate Immunity in Disease and Adaptation to Stress
Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last decades point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation.
  • 693
  • 06 Jun 2022
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.
  • 691
  • 03 Mar 2022
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