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Topic Review
Exploitation of Neutrophil Functions to Combat Disease
Neutrophils are crucial innate immune cells and comprise 50–70% of the white blood cell population under homeostatic conditions. Upon infection and in cancer, blood neutrophil numbers significantly increase because of the secretion of various chemo- and cytokines by, e.g., leukocytes, pericytes, fibroblasts and endothelial cells present in the inflamed tissue or in the tumor microenvironment (TME). The function of neutrophils in cancer has recently gained considerable attention, as they can exert both pro- and anti-tumorigenic functions, dependent on the cytokine milieu present in the TME. Here, several promising therapeutic options are addressed, such as cytokine therapy, immunocytokines and immunotherapy, which aim to exploit the anti-tumorigenic potential of neutrophils in cancer treatment or block excessive neutrophil-mediated inflammation in autoimmune diseases.
  • 272
  • 16 Aug 2023
Topic Review
lncRNAs in NF-κB-Mediated Macrophage Inflammation
Molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity.
  • 271
  • 12 Mar 2024
Topic Review
Crosstalk between ILC3s and Microbiota
In recent years, growing evidence has suggested that the gut microbiome can significantly influence antitumor immunity, both within and outside the gastrointestinal tract, thereby affecting the efficacy of immune checkpoint inhibitors (ICIs). A link between microbiota composition and response to ICIs has been reported in both mouse and human studies. Gut microbial features depend on a delicate balance of tolerance for commensal microbiota and defense against various potentially pathogenic microbiota orchestrated by host immune system. Type 3 innate lymphoid cells (ILC3s) are a group of tissue-resident innate lymphocytes related to host immune cell–microbiome interactions. They orchestrate immunity, inflammation and tolerance in the intestines and any alterations in their functions can cause gut inflammation, colon cancer and immunotherapy resistance.
  • 270
  • 05 Sep 2023
Topic Review
Intestinal Microbiota in Cancer Immunotherapy
Despite the great achievements of cancer immunotherapy in a variety of tumors, tumor heterogeneity and drug resistance still plague patients and clinical researchers. In particular, the occurrence of immune-related adverse events forces patients to discontinue cancer immunotherapy. Therefore, it is urgent to optimize cancer immunotherapy and improve the efficacy of immunotherapy. With the iteration of sequencing technology, the microbiome, as the second set of genomes in the body, has been proven to be involved in immunity and metabolism. More and more studies are gradually shifting the perspective to the intestinal microbiota and cancer immunotherapy. The intestinal microbiota reactivates and modulates immune cells in immunotherapy and is expected to become a biomarker for predicting immune efficacy. Targeting to improve the intestinal microbiota can enhance anti-tumor immunity. This advantage is beneficial to control related adverse symptoms and expand the beneficiary population of cancer immunotherapy. This finding can help clinicians comprehensively evaluate the effect of tumor screening and tumor treatment. Therefore, the innovative combination of gut microbiota and cancer immunotherapy is expected to be an active strategy to enhance individualized immune responses. 
  • 269
  • 12 Oct 2022
Topic Review
Impact of Glioblastomas-Derived Extracellular Vesicles on Macrophage Function
Glioblastomas (GBM) are a devastating disease with extremely poor clinical outcomes. Resident (microglia) and infiltrating macrophages are a substantial component of the tumor environment. In GBM and other cancers, tumor-derived extracellular vesicles (EVs) suppress macrophage inflammatory responses, impairing their ability to identify and phagocytose cancerous tissues. Furthermore, these macrophages then begin to produce EVs that support tumor growth and migration. This cross-talk between macrophages/microglia and gliomas is a significant contributor to GBM pathophysiology.
  • 269
  • 02 Jun 2023
Topic Review
Pathogenesis and Diagnosis of Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic, chronic, autoimmune disease categorized by synovial inflammation due to the infiltration of T cells, B cells, neutrophils, and macrophages, destroying articular joints and bone architecture. RA is primarily associated with inflammation within synovial joints. All peripheral joints can be affected in RA, but the most affected are those of the hands, feet, and knees. Although RA’s etiology is still unknown, several factors contributing to RA have been identified. Among them are the susceptibility genes, disease-causing immune cells, and cytokine and signal transduction networks that promote inflammation.
  • 268
  • 07 Nov 2023
Topic Review
Chimeric Antigen Receptor T Cell Therapy in AML
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is being investigated in AML.
  • 267
  • 19 Jan 2024
Topic Review
Innate Immunity in Tumor Microenvironment
Immunotherapies including adaptive immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have developed the treatment of cancer in clinic, and most of them focus on activating T cell immunity. Although these strategies have obtained unprecedented clinical responses, only limited subsets of cancer patients could receive long-term benefits, highlighting the demand for identifying novel targets for the new era of tumor immunotherapy. Innate immunity has been demonstrated to play a determinative role in the tumor microenvironment (TME) and influence the clinical outcomes of tumor patients.
  • 264
  • 12 Jul 2023
Topic Review
Novel Therapies in Glioblastoma Treatment
One of the most prevalent primary malignant brain tumors is glioblastoma (GB). About 6 incidents per 100,000 people are reported annually. Most frequently, these tumors are linked to a poor prognosis and poor quality of life. There has been little advancement in the treatment of GB. In recent years, some innovative medicines have been tested for the treatment of newly diagnosed cases of GB and recurrent cases of GB. Surgery, radiotherapy, and alkylating chemotherapy are all common treatments for GB. A few of the potential alternatives include immunotherapy, tumor-treating fields (TTFs), and medications that target specific cellular receptors. To provide new multimodal therapies that focus on the molecular pathways implicated in tumor initiation and progression in GB, novel medications, delivery technologies, and immunotherapy approaches are being researched. Of these, oncolytic viruses (OVs) are among the most recent. Coupling OVs with certain modern treatment approaches may have significant benefits for GB patients. 
  • 263
  • 29 Dec 2023
Topic Review
Electroceutical Therapy for Autoimmune Disease
Continuous dialogue between the immune system and the brain plays a key homeostatic role in various immune responses to environmental cues. Several functions are under the control of the vagus nerve-based inflammatory reflex, a physiological mechanism through which nerve signals regulate immune functions. In the cholinergic anti-inflammatory pathway, the vagus nerve, its pivotal neurotransmitter acetylcholine, together with the corresponding receptors play a key role in modulating the immune response of mammals. Bioelectronic medicine has recently emerged as an alternative approach to managing systemic inflammation. Nerve electrostimulation was reported to be clinically relevant in reducing chronic inflammation in autoimmune diseases, including rheumatoid arthritis and diabetes.
  • 262
  • 18 Aug 2023
Topic Review
Ovarian Cancer Immunogenicity
Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The disease is often diagnosed after wide-spread dissemination, and the standard treatment combines aggressive surgery with platinum-based chemotherapy; however, most patients experience relapse in the form of peritoneal carcinomatosis, resulting in a 5-year mortality below 45%. There is clearly a need for the development of novel treatments and cancer immunotherapies offering a different approach. Immunotherapies have demonstrated their efficacy in many types of cancers; however, only <15% of EOC patients show any evidence of response. One of the main barriers behind the poor therapeutic outcome is the reduced expression of Major Histocompatibility Complexes class I (MHC I) which occurs in approximately 60% of EOC cases. 
  • 254
  • 26 Dec 2023
Topic Review
Dendritic Cells Function in Antitumor Responses
High-grade gliomas are malignant brain tumors, and patient outcomes remain dismal despite the emergence of immunotherapies aimed at promoting tumor elimination by the immune system. A robust antitumor immune response requires the presentation of tumor antigens by dendritic cells (DC) to prime cytolytic T cells. 
  • 253
  • 15 Aug 2023
Topic Review
Neurotrophic Virus and Systemic Lupus Erythematosus Development
Neurotrophic viruses are pathogens that can cause alterations in the function of the central nervous system (CNS). These viruses can enter the CNS through the previously mentioned pathways. Additionally, it has been observed that viruses whose genome corresponds to RNA can be introduced into the CNS through nerves, such as the sciatic nerve. Some can even transport immune cells, allowing them to arrive at the CNS. On the other hand, double-stranded DNA (dsDNA) viruses can enter the CNS by penetrating the blood–brain barrier, utilizing brain microvascular endothelial cells, and even using sensory nerve endings and olfactory receptor neurons to enter the CNS. When the infection occurs, the main mechanism that the CNS possesses to defend itself is the activation of microglia, which induce the activation of the innate immune response and a subsequent adaptive immune response. Even the microglia can act with astrocytes to induce the chemotaxis of immune cells, like neutrophils, to combat infection generated in the CNS.
  • 252
  • 12 Jan 2024
Topic Review
Host Immune Responses to Trypanosomes
The mammalian host’s innate and adaptive immune systems are both key to successfully resisting or controlling trypanosomosis. When trypanosomes are inoculated into the mammalian hosts by a blood-feeding insect such as a tsetse fly, the first contact between the trypanosome and host occurs in the skin. Here, a chancre often develops at the dermal inoculation site. Intense innate immune reactions, cellular reactions, and edema formation accompany these chancres. Thereafter, parasites start to circulate through the blood or lymph, invading lymphatic tissues and various organs. There, the trypanosomes again encounter various innate immune components before being confronted with the adaptive immune system. Once entered into the circulation stage of infection, trypanosomes are going to encounter responses from macrophages and B cells, as well as the T helper compartment that links these two.
  • 251
  • 07 Mar 2024
Topic Review
The Effects of Dietary on Tumor Metabolism
The remodeled cancer cell metabolism affects the tumor microenvironment and promotes an immunosuppressive state by changing the levels of macro- and micronutrients and by releasing hormones and cytokines that recruit immunosuppressive immune cells. Novel dietary interventions such as amino acid restriction and periodic fasting mimicking diets can prevent or dampen the formation of an immunosuppressive microenvironment by acting systemically on the release of hormones and growth factors, inhibiting the release of proinflammatory cytokines, and remodeling the tumor vasculature and extracellular matrix.
  • 250
  • 10 Aug 2023
Topic Review
Role of Neutrophils in Immune-Related Diseases
Neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation. Neutrophils are a heterogeneous group of immune cells from which are derived extracellular traps (NETs), reactive oxygen species, cytokines, chemokines, immunomodulatory factors, and alarmins that regulate the recruitment and phenotypes of neutrophils, macrophages, dendritic cells, T cells, and B cells. In addition, cytokine-stimulated neutrophils can express class II major histocompatibility complex and the internal machinery necessary for successful antigen presentation to memory CD4+ T cells. This may be relevant in the context of vaccine memory. Neutrophils thus emerge as orchestrators of immune responses that play a key role in determining the outcome of infections, vaccine efficacy, and chronic diseases like autoimmunity and cancer.
  • 247
  • 09 Jan 2024
Topic Review
ATF3 in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection
Transcription factors are pivotal regulators in the cellular life process. Activating transcription factor 3 (ATF3), a member of the ATF/CREB (cAMP response element-binding protein) family, plays a crucial role as cells respond to various stresses and damage. As a transcription factor, ATF3 significantly influences signal transduction regulation, orchestrating a variety of signaling pathways, including apoptosis, ferroptosis, and cellular differentiation. In addition, ATF3 serves as an essential link between inflammation, oxidative stress, and immune responses. 
  • 246
  • 20 Feb 2024
Topic Review
Single-Cell Transcriptomics of Mtb/HIV Co-Infection
Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection continues to pose a significant healthcare burden. HIV co-infection during TB predisposes the host to the reactivation of latent TB infection (LTBI), worsening disease conditions and mortality. There is a lack of biomarkers of LTBI reactivation and/or immune-related transcriptional signatures to distinguish active TB from LTBI and predict TB reactivation upon HIV co-infection. Characterizing individual cells using next-generation sequencing-based technologies has facilitated novel biological discoveries about infectious diseases, including TB and HIV pathogenesis.
  • 246
  • 27 Sep 2023
Topic Review
IL-23 in Autoimmune Fibrotic Diseases
Interleukin (IL)-23 is a central pro-inflammatory cytokine with a broad range of effects on immune responses. IL-23 is pathologically linked to the induction of the production of the pro-inflammatory cytokines IL-17 and IL-22, which stimulate the differentiation and proliferation of T helper type 17 (Th17) cells. Discoveries suggest a potential pro-fibrotic role for IL-23 in the development of chronic inflammatory autoimmune diseases characterized by intense fibrosis.
  • 245
  • 15 Sep 2023
Topic Review
Staphylococcus aureus-Derived Extracellular Vesicles and Atopic Dermatitis Pathophysiology
Atopic dermatitis (AD) is a chronic and relapsing inflammatory cutaneous disease. The role of host defense and microbial virulence factors in Staphylococcus aureus skin colonization, infection, and inflammation perpetuation in AD remains an area of current research focus. Extracellular vesicles (EV) mediate cell-to-cell communication by transporting and delivering bioactive molecules, such as nucleic acids, proteins, and enzymes, to recipient cells. Staphylococcus aureus spontaneously secretes extracellular vesicles (SA-derived EVs), which spread throughout the skin layers. Research has shown that SA-derived EVs from AD patients can trigger cytokine secretion in keratinocytes, shape the recruitment of neutrophils and monocytes, and induce inflammatory AD-type lesions in mouse models, in addition to their role as exogenous worsening factors for the disease. 
  • 245
  • 22 Mar 2024
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