Role Of Immune System Research Articles

Characteristics of immune cells and causal relationship with chondromalacia: A two-sample, bidirectional mendelian randomization study.

Chondromalacia, characterized by the softening of cartilage, is a prevalent condition affecting joint health with complex etiology. The immune system's role in its pathogenesis has been implicated but remains to be fully elucidated. To address a critical knowledge gap, we conducted a two-sample Mendelian randomization analysis of 731 immune cell phenotypes, assessing parameters like fluorescence, cell count, and morphology. After sensitivity and pleiotropy checks, and applying a false discovery rate correction, our study linked 17 phenotypes to chondromalacia (p < .05). Among them, seven immune cell phenotypes were found to have a protective effect against chondromalacia (IVW: p < .05, OR <1), while 10 were considered risk factors (IVW:p < .05, OR >1). Despite the constraints of sample size and possible genetic differences among populations, our research has identified a notable genetic correlation between specific immune cell indicators and chondromalacia. This breakthrough sheds light on the pathophysiological mechanisms of the condition. The identification of protective and risk-associated immune cell phenotypes provides a foundation for further exploration of immunological mechanisms in chondromalacia and may pave the way for targeted interventions. Future research is warranted to validate these findings and explore their clinical implications.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. Statement of significanceMalignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis.

Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system's role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.

Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system.

Cancer immunotherapies include monoclonal antibodies, cytokines, oncolytic viruses, cellular therapies, and other biological and synthetic immunomodulators. These are traditionally studied for their effect on the immune system's role in eliminating cancer cells. However, some of these therapies have the unique ability to directly induce cytotoxicity in cancer cells by inducing immunogenic cell death (ICD). Unlike general immune stimulation, ICD triggers specific therapy-induced cell death pathways, based on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells. These activate innate pattern recognition receptors (PRRs) and subsequent adaptive immune responses, offering the promise of sustained anticancer drug efficacy and durable antitumour immune memory. Exploring how onco-immunotherapies can trigger ICD, enhances our understanding of their mechanisms and potential for combination strategies. This review explores the complexities of these immunotherapeutic approaches that induce ICD, highlighting their implications for the innate immune system, addressing challenges in cancer treatment, and emphasising the pivotal role of ICD in contemporary cancer research.

The Immune System's Role In Longer Multiple Myeloma Remission

The Immune System's Role In Longer Multiple Myeloma Remission

Safety and efficacy of immune checkpoint inhibitors after allogeneic hematopoietic cell transplantation.

The immune system plays a major role in preventing infections and cancers. Impairment in immunity may facilitate the development of neoplasia owing to defective immune surveillance, among other mechanisms. Immune evasion plays a significant role in relapse after allogeneic hematopoietic cell transplantation (alloHCT); one purported mechanism is through immune checkpoint signaling pathways. Checkpoint inhibitors (CPIs) are FDA approved for relapsed classical Hodgkin's Lymphoma (cHL), primary mediastinal large B cell Lymphoma (PMBCL) and other solid tumors. Retrospective studies evaluating the outcomes of alloHCT after prior exposure to CPIs showed favorable survival outcomes but high rates of graft-versus-host disease (GVHD); the risk appears to be lower when using post-transplant cyclophosphamide as GVHD prophylaxis. CPIs have increasingly been used to prevent or treat post-alloHCT relapse. Available data, albeit limited, supports the clinical activity of CPIs in post-alloHCT relapse; however, serious and even fatal cases of GVHD have been reported. The optimal timing, schedule, dosing, and patients likely to benefit from this strategy are yet to be identified. In this review, we highlight the immune system's role in cancer surveillance and relapse prevention and discuss the current clinical evidence of CPIs use in post-alloHCT relapse.

Identification of serum immunoglobulin M (IgM) of crucian carp (Carassius auratus gibelio) and immune response to cyprinid herpesvirus 2 infection

Crucian carp (Carassius auratus gibelio), an extensively cultivated freshwater fish, was one of the model species for the study of fish immunology. Polyclonal antibodies were advantageous molecular tools for studying teleost immune system. Specifically, polyclonal antibodies reacting with immunoglobulins (Ig) were used successfully in studies of the teleost fishes. In the present study, we produced polyclonal antibody against CH2 domains of crucian carp IgM, and measured the in vivo dynamics of IgM mRNA caused by CyHV-2 infection. The recombinant protein IgM with relative molecular weight about 53 KD was correctly expressed in prokaryotic cells. The specificity of the polyclonal antibody was evaluated by Western blotting and results revealed that the antibody not only specifically recognized crucian carp serum but also cross-reacted with grass carp serum. Quantitative RT-PCR analysis demonstrated the expression of IgM mRNA changed significantly after CyHV-2 infection. The expression of IgM in the kidney increased and reached a maximum at 6 h post-infection (hpi), while dropped to a low level at 5 days post-infection (dpi). In conclusion, the expression of IgM was significantly upregulated in the kidney of crucian carp infected with CyHV-2, indicating that IgM played a potential role in systemic immunity against viral infection. Polyclonal antibody against crucian carp IgM had certain clinical relevance, which might provide insight into the early stage of virus infection and prevention of the disease.

The efficacy of the benzimidazoles oxfendazole and flubendazole against Litomosoides sigmodontis is dependent on the adaptive and innate immune system.

Filarial nematodes can cause debilitating diseases such as lymphatic filariasis and onchocerciasis. Oxfendazole (OXF) is one promising macrofilaricidal candidate with improved oral availability compared to flubendazole (FBZ), and OXF is currently under preparation for phase 2 clinical trials in filariasis patients. This study aimed to investigate the immune system's role during treatment with OXF and FBZ and explore the potential to boost the treatment efficacy via stimulation of the immune system. Wild type (WT) BALB/c, eosinophil-deficient ΔdblGata1, IL-4r/IL-5-/-, antibody-deficient μMT and B-, T-, NK-cell and ILC-deficient Rag2/IL-2rγ-/- mice were infected with the rodent filaria Litomosoides sigmodontis and treated with an optimal and suboptimal regimen of OXF and FBZ for up to 5 days. In the second part, WT mice were treated for 2-3 days with a combination of OXF and IL-4, IL-5, or IL-33. Treatment of WT mice reduced the adult worm burden by up to 94% (OXF) and 100% (FBZ) compared to vehicle controls. In contrast, treatment efficacy was lower in all immunodeficient strains with a reduction of up to 90% (OXF) and 75% (FBZ) for ΔdblGata1, 50 and 92% for IL-4r/IL-5-/-, 64 and 78% for μMT or 0% for Rag2/IL-2rγ-/- mice. The effect of OXF on microfilariae and embryogenesis displayed a similar pattern, while FBZ's ability to prevent microfilaremia was independent of the host's immune status. Furthermore, flow cytometric analysis revealed strain-and treatment-specific immunological changes. The efficacy of a shortened 3-day treatment of OXF (-33% adult worms vs. vehicle) could be boosted to a 91% worm burden reduction via combination with IL-5, but not IL-4 or IL-33. Our results suggest that various components of the immune system support the filaricidal effect of benzimidazoles in vivo and present an opportunity to boost treatment efficacy.

The role of systemic immunity in ALS: a population-based study (P8-8.006)

The role of systemic immunity in ALS: a population-based study (P8-8.006)

Abstract 2343: Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma

Abstract Ependymoma is a common type of brain tumor in children, often resistant to available cytotoxics. Molecular profiling studies have led to a better understanding of ependymoma pathology and revealed a critical role of EPHB2. However, the immune system's role in tumor progression and treatment response remains poorly understood. Here, we show that the multikinase inhibitor dasatinib potently inhibits EPHB2 and ABL1 and the growth of ependymoma both in vitro and in vivo. Using an immunocompetent mouse model of ependymoma that faithfully recapitulates its immune microenvironment, we found an increased frequency of M2-like tumor-associated macrophages (TAMs), which proportionally increased with tumor size. Treatment with dasatinib reprogrammed the immune microenvironment of ependymoma by polarizing the TAMs toward an M1-like phenotype and increasing CD8 T cell activation. Dasatinib treatment induced complete regression of established mEPN-Ephb2 tumors in 78% of the animals and protected survivors against tumor recurrence. These studies indicate that dasatinib may be an effective therapy for this molecular subgroup of pediatric brain tumors and should be tested in clinical trials. Citation Format: Jun Ren, Zohreh Amoozgar, Yuhui Zhao, Pinji Lei, William W. Ho, Sylvie Robergea, Peigen Huang, Dan G. Duda, Lei Xu, Rakesh K. Jain. Targeting EPHB2/ABL1 restores anti-tumor immunity in a preclinical model of ependymoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2343.

Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer.

The immune system's role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7weeks, range 8.1-25.1weeks for the prospective cohort and 5.3weeks with a range of 2.7-9.0weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier'd at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity.

Toll-like receptor 7 regulates cardiovascular diseases.

Cardiovascular disease (CVD) is the major leading cause of morbidity and mortality worldwide. According to the pro-inflammatory nature of CVD, recent studies highlighted the immune system's role in its pathogenesis and development. Toll-like receptors (TLRs) have been identified as dominant innate immune receptors. TLR-7 is an intracellular receptor expressed on endosomes or cytoplasmic reticulum and is responsible for detecting damage-associated molecular patterns, which are remarkable during inflammation and viral infection. In addition to immune cells, TLR-7 is expressed in endothelial cells, vascular smooth muscle cells, and platelets. TLR-7 ligands are single-stranded ribonucleic acid (ssRNA) and short interfering RNA, which can activate the signaling pathway and lead to both inflammatory (e.g., interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor- α (TNF-α)) and anti-inflammatory (e.g., IL-10) cytokines release. By growing evidence, it has been proven that TLR-7 activated platelets can increase the risk of thrombus formation by neutrophil aggregation. At the same time, they have a protective role against thrombosis by releasing granulocyte-macrophage colony-stimulating factors. The same two-sided effect was observed between TLR-7 and atherosclerotic plaque formation. Moreover, recent studies explained an association between TLR-7 activation and increased risk of complete heart block, myocarditis, left ventricular remodeling, and rupture. Here we review the rapid progress that has been made in this field, which has improved our understanding of TLR-7 function in CVDs, and discuss the current treatments targeting this receptor.

Reducing decoys focuses fighting microglia.

Genetic variation linked to lower levels of soluble ST2, a decoy cytokine receptor for IL-33, may protect against Alzheimer's disease in female APOEε4 carriers by increasing microglial plaque removal. This discovery advances our understanding of the immune system's role in Alzheimer's disease and underscores the importance of sex-specific disease processes.

The immune system's role in PCOS.

Polycystic ovary syndrome (PCOS) is a common disorder of the endocrine system. Its main manifestations include oligo-ovulation, hyperandrogenism, and polycystic ovary morphology (PCOM), affecting women of childbearing age. Although the exact pathogenesis of this disease is still unknown, many factors, including genetic, endocrine, and metabolism disorders, play critical roles in its development. The immunopathogenesis of PCOS has not yet been studied in-depth, but it is hypothesized that immune system abnormalities may play a key role in it. Recent research has shown inflammation's effect on ovulation and ovarian follicular dynamics. Thus, it is suggested that there is a close association between PCOS and low-grade chronic systemic inflammation. As a result, chronic low-grade inflammation is identified as a significant factor in the pathogenesis and development of PCOS, which in turn leads to infertility. As a result, this article reviews PCOS immunopathology, evaluates long-standing hypotheses about the immune system's role in PCOS, and assesses the association between inflammatory factors and PCOS.

Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles.

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Systematic Review and Pooled Analysis of the Impact of Treatment-Induced Lymphopenia on Survival of Glioblastoma Patients

Lymphopenia is a known toxicity of chemotherapy and radiation therapy (RT), part of the standard treatment for glioblastoma (GBM). Given the immune system's role in cancer control and general health, a number of single-institution studies have examined the association between treatment-related lymphopenia and survival outcomes of GBM patients. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemoRT.Following PRISMA guidelines, a systematic review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. Inclusion criteria included: (1) retrospective/prospective studies of human subjects (2) GBM patients (3) treated with chemoRT (4) reported lymphopenia and OS outcomes (5) analyzed lymphopenia and OS association. Analysis was conducted using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS.104 studies were identified, with 11 studies meeting the inclusion criteria, representing 2,196 unique patients. The threshold of lymphopenia varied between studies (lymphocyte count cutoff value range of 400 - 1200 cells/uL; mode 500 cell/uL). The time of lymphopenia onset was dichotomized into two groups (time-point vs time-range), with 6 studies tabulating the incidence of lymphopenia defined at a fixed time point approximately 2-months after the start of RT, while 5 studies utilized a time-range, tabulating the incidence of lymphopenia defined as any occurrence of lymphopenia from the start of RT to approximately 2-months after the start of RT. The mean overall pooled incidence of lymphopenia for all 11 studies was 32.4%, and was 21.1% vs 41% for time-point studies and time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI: 1.46 - 2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI: 1.24 - 1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies (P = 0.6 for time-point and P = 0.5 for time-range studies). Available pooled analysis of MVA estimates of HR for the time-range studies were confirmatory, with pooled HR of 1.36 (95% CI: 1.12 - 1.65, P < 0.002), with significant heterogeneity between studies, P = 0.02.These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between treatment-related lymphopenia with decreased OS in GBM patients, highlighting lymphopenia as a poor prognostic factor. These results are hypothesis generating, stimulating a better understanding regarding causality and underscores the need for investigations into strategies to mitigate lymphopenia. Such insights may improve outcomes and possibly shed light on the limited efficacy of immunotherapy for the treatment of GBM.A. Saeed: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. M.V. Mishra: Employee; Orthofix. Research Grant; ASTRO, Keep Punching. Advisory Board; Patient Centers Outcomes Research Institute (PCORI. Travel Expenses; Patient Centers Outcomes Research Institute (PCORI.

The pathophysiology of immunoporosis: innovative therapeutic targets

The physiological balance between bone resorption and bone formation is now known to be mediated by a cascade of events parallel to the classic osteoblast-osteoclast interaction. Thus, osteoimmunology now encompasses the role played by other cell types, such as cytokines, lymphocytes and chemokines, in immunological responses and how they help modulate bone metabolism. All these factors have an impact on the RANK/RANKL/OPG pathway, which is the major pathway for the maturation and resorption activity of osteoclast precursor cells, responsible for osteoporosis development. Recently, immunoporosis has emerged as a new research area in osteoimmunology dedicated to the immune system's role in osteoporosis. The first part of this review presents theoretical concepts on the factors involved in the skeletal system and osteoimmunology. Secondly, existing treatments and novel therapeutic approaches to treat osteoporosis are summarized. These were selected from to the most recent studies published on PubMed containing the term osteoporosis. All data relate to the results of in vitro and in vivo studies on the osteoimmunological system of humans, mice and rats. Treatments for osteoporosis can be classified into two categories. They either target osteoclastogenesis inhibition (denosumab, bisphosphonates), or they aim to restore the number and function of osteoblasts (romozumab, abaloparatide). Even novel therapies, such as resolvins, gene therapy, and mesenchymal stem cell transplantation, fall within this classification system. This review presents alternative pathways in the pathophysiology of osteoporosis, along with some recent therapeutic breakthroughs to restore bone homeostasis.

Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease.

The immune system's role is much more than merely recognizing self vs. non-self and involves maintaining homeostasis and integrity of the organism starting from early development to ensure proper organ function later in life. Unlike other systems, the central nervous system (CNS) is separated from the peripheral immune machinery that, for decades, has been envisioned almost entirely as detrimental to the nervous system. New research changes this view and shows that blood-borne immune cells (both adaptive and innate) can provide homeostatic support to the CNS via neuroimmune communication. Neurodegeneration is mostly viewed through the lens of the resident brain immune populations with little attention to peripheral circulation. For example, cognition declines with impairment of peripheral adaptive immunity but not with the removal of microglia. Therapeutic failures of agents targeting the neuroinflammation framework (inhibiting immune response), especially in neurodegenerative disorders, call for a reconsideration of immune response contributions. It is crucial to understand cross-talk between the CNS and the immune system in health and disease to decipher neurodestructive and neuroprotective immune mechanisms for more efficient therapeutic strategies.

The hipotises of the immune system's role in carcinogenesis

The presented controversial hypothesis is an attempt to reflect on the role of the adaptive immune response in carcinogenesis. It is a well-known fact that the most of the signaling pathways which are participating in embryogenesis and regeneration are also active in tumor growth. Considering their presence in different evolutionary groups, there's such a contradiction that with same mechanisms of proliferation, animals with high regenerative potential are less predisposed to malignancy than mammals. Comparing these two groups, it's being discovered that despite the importance of immune control as a factor impeding carcinogenesis, the animals' immune system with high regenerative potential is less developed. The above is a reading of the complete or partial absence of the adaptive link of immunity. These described distinctions have formed the basis of the hypothesis of the procarcino-genic role of the adaptive immune response.

The Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion).

Mild traumatic brain injury (mild TBI), often referred to as concussion, is the most common form of TBI and affects millions of people each year. A history of mild TBI increases the risk of developing emotional and neurocognitive disorders later in life that can impact on day to day living. These include anxiety and depression, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD). Actions of brain resident or peripherally recruited immune cells are proposed to be key regulators across these diseases and mood disorders. Here, we will assess the impact of mild TBI on brain and patient health, and evaluate the recent evidence for immune cell involvement in its pathogenesis.