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Topic Review
Pyroptosis and Cervical Cancer
Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. The morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women’s health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer.
  • 744
  • 30 Nov 2022
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. 
  • 741
  • 14 Nov 2022
Topic Review
Species of Gut Bacteria Associated with Antitumor Immunity
Both preclinical and clinical studies have demonstrated that the modulation of gut microbiota could be a promising strategy for enhancing antitumor immune responses and reducing resistance to immunotherapy in cancer. Various mechanisms, including activation of pattern recognition receptors, gut commensals-produced metabolites and antigen mimicry, have been revealed. Different gut microbiota modulation strategies have been raised, such as fecal microbiota transplantation, probiotics, and dietary selection.
  • 741
  • 02 Dec 2022
Topic Review
Eminent Role of β2-AR in T Cells
Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis.
  • 739
  • 31 Aug 2023
Topic Review
Role of PPARα in the Gastrointestinal Mucosa
Peroxisome proliferator-activated receptor alpha (PPARα) is expressed throughout the mammalian gut: in epithelial cells, in the villi of enterocytes and in Paneth cells of intestinal crypts, as well as in some immune cells (e.g., lamina propria macrophages, dendritic cells) of the mucosa.  The Ppara transcription quantification in villus-crypt axis showed that the highest expression is observed in the peaks of villi of the middle part between duodenum and ileum of murine intestine. 
  • 736
  • 05 Dec 2022
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. 
  • 736
  • 24 May 2023
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. 
  • 733
  • 02 Feb 2021
Topic Review
Lymphatic Clearance of Immune Cells in Cardiovascular Disease
The lymphatic vasculature is a vital component of the cardiovascular system, consisting of a blind-ended, highly permeable vascular network, integral in maintaining tissue homeostasis, regulation of interstitial fluid, lipid absorption, fluid drainage, and immune cell trafficking. Its role in immune cell transport is critical in the initiation of the immune response, especially following injury. This is of particular importance in the heart, where the lymphatic vasculature plays a vital role in myocardial healing following cardiac injury. By promoting cell egress or exit from the heart, the lymphatic systems favour cell clearance by way of reduction of the immune cell load in damaged tissue.
  • 733
  • 13 Apr 2022
Topic Review
Approaches to Enhance Tumor Antigenicity
Cancer immunotherapy has revolutionized the oncology field, but many patients still do not respond to the immunotherapy approaches. One of the main challenges in broadening the range of responses to this type of treatment is the limited source of tumor neoantigens. New approaches must be taken into consideration to overcome these shortcomings. The possibility of making tumors more antigenic represents a promising front to further improve the success of immunotherapy in cancer. 
  • 731
  • 09 Sep 2022
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.
  • 730
  • 28 Apr 2021
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.
  • 730
  • 22 Feb 2022
Topic Review
Natural Killer Cells in Liver Fibrosis
Natural killer (NK) cells are a key component of innate immunity and have miscellaneous roles in liver health and disease. Accumulating evidence shows that NK cells play dual roles in the development and progression of liver fibrosis, including profibrotic and anti-fibrotic functions.
  • 730
  • 18 May 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.
  • 728
  • 21 Dec 2021
Topic Review
Synergism of Radiotherapy, PARP Inhibition, and Immune-Checkpoint Blockade
Radiotherapy and, more recently, PARP inhibitors (PARPis) and immune-checkpoint inhibitors represent effective tools in cancer therapy. Radiotherapy exerts its effects not only by damaging DNA and inducing tumor cell death, but also stimulating anti-tumor immune responses. PARPis are known to exert their therapeutic effects by inhibiting DNA repair, and they may be used in combination with radiotherapy. Both radiotherapy and PARPis modulate inflammatory signals and stimulate type I IFN (IFN-I)-dependent immune activation. However, they can also support the development of an immunosuppressive tumor environment and upregulate PD-L1 expression on tumor cells. When provided as monotherapy, immune-checkpoint inhibitors (mainly antibodies to CTLA-4 and the PD-1/PD-L1 axis) result particularly effective only in immunogenic tumors. Combinations of immunotherapy with therapies that favor priming of the immune response to tumor-associated antigens are, therefore, suitable strategies. The widely explored association of radiotherapy and immunotherapy has confirmed this benefit for several cancers. Association with PARPis has also been investigated in clinical trials. Immunotherapy counteracts the immunosuppressive effects of radiotherapy and/or PARPis and synergies with their immunological effects, promoting and unleashing immune responses toward primary and metastatic lesions (abscopal effect). 
  • 727
  • 22 Feb 2023
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.
  • 727
  • 29 Jun 2023
Topic Review
Bovine Immunity and Vitamin D3
Mycobacterium avium subspecies paratuberculosis (MAP) is an environmentally hardy pathogen of ruminants that is transmitted via the fecal-oral route. Transition from subclinical to clinical infection is a dynamic process led by MAP, which survives and replicates in host macrophages. Hallmark clinical symptoms include granulomatous enteritis, watery diarrhea, and significant loss of body condition. Clinical stage disease is accompanied by dysfunctional immune responses and a reduction in circulating vitamin D3. The immunomodulatory role of vitamin D3 in infectious disease has been well established in humans, particularly in Mycobacterium tuberculosis infection. However, significant species differences exist between the immune system of humans and bovines, including effects induced by vitamin D3. 
  • 726
  • 27 Sep 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. 
  • 724
  • 07 Dec 2021
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.
  • 722
  • 30 Jun 2021
Topic Review
Myocardial Infarction Guided Emergency Hematopoiesis
“Emergency hematopoiesis” occurs after myocardial infarction (MI) and includes different processes: (1) the amplification of leukocyte production, (2) the maturation of alternative leukocyte subsets and (3) the release of myeloid cells from primary and secondary hematopoietic organs.
  • 722
  • 22 Dec 2022
Topic Review
M.tb PE_PGRS Acts as an Immunological Decoy
Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.
  • 717
  • 18 Jan 2022
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