Progress In Immunology Research Articles

Tumor Immunology Unveiled: Advances, Challenges, and Future Prospects in Cancer Immunotherapy

Among the most important disciplines in the field of immunology, tumor immunology holds a significant place due to its focus on the interaction between tumors and the immune system. With the advancement of immunotherapy technologies in recent years, tumor immunology has emerged as one of the most exciting areas in cancer research. In this article, we will examine in detail the research progress in tumor immunology, including the mechanisms by which tumor cells evade the immune system, the application of immune checkpoint inhibitors, the development of tumor vaccines and their application in clinical practice, and how the tumor microenvironment impacts immunotherapy.

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p<0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p<0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p<0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p<0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p<0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p<0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease.

Antiviral potential of spirulina in individuals with human immunodeficiency virus or Hepatis C virus infections: A systematic review and meta-analysis

BackgroundSpirulina, a cyanobacterium or blue-green algae that contains phycocyanin, nutritional supplementation has been evaluated in patients living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) due to its antiviral properties. This supplementation may be beneficial in low resource settings when awaiting antiretroviral therapy (ART) for HIV. This review aimed to evaluate the effectiveness of Spirulina supplement in antiviral-naïve HIV- and HCV-infected patients by assessing its immunological effect (Cluster of Differentiation 4 or CD-4 T-cell count) and disease progression (viral load). MethodsWe searched PubMed, Cochrane Library, Scopus, and Web of Science from inception through January 23, 2024. Two authors independently performed the study selection, data extraction, and risk of bias assessment. We pooled data by using a random-effects model and evaluated publication bias by a funnel plot. ResultsWe identified 5552 articles, 5509 excluded at the title and abstract stage with 44 studies making it to the full text review. Of these 6 studies met the eligibility for inclusion in the final analysis as follows:4 randomized controlled trials (RCTs) and 2 non-RCTs. The pooled results of the Spirulina intervention found significant improvements in biomarkers of clinical outcomes, viral load (VL) and CD4 T-cell (CD4) counts, in participants of the treatment group compared to controls; the VL had an overall Cohen’s d effect size decrease of -2.49 (-4.80, -0.18) and CD4 had an overall effect size increase of 4.09 (0.75, 7.43). [Cohen’s d benchmark: 0.2 = small effect; 0.5 = medium effect; 0.8 = large effect]. ConclusionsFindings from this systematic review showed a potential beneficial effect of Spirulina supplementation in HIV- and HCV-infected patients by increasing CD4 counts and decreasing viral load. However, further research in larger controlled clinical trials is needed to fully investigate the effect of this nutritional supplement on clinically relevant outcomes, opportunities for intervention, optimal dose, and cost-benefit of Spirulina supplementation.

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic.

Autism spectrum disorder (ASD1) is a behaviorally defined syndrome encompassing a markedly heterogeneous patient population. Many ASD subjects fail to respond to the 1st line behavioral and pharmacological interventions, leaving parents to seek out other treatment options. Evidence supports that neuroinflammation plays a role in ASD pathogenesis. However, the underlying mechanisms likely vary for each ASD patient, influenced by genetic, epigenetic, and environmental factors. Although anti-inflammatory treatment measures, mainly based on metabolic changes and oxidative stress, have provided promising results in some ASD subjects, the use of such measures requires the careful selection of ASD subjects based on clinical and laboratory findings. Recent progress in neuroscience and molecular immunology has made it possible to allow re-purposing of currently available anti-inflammatory medications, used for autoimmune and other chronic inflammatory conditions, as treatment options for ASD subjects. On the other hand, emerging anti-inflammatory medications, including biologic and gate-keeper blockers, exert powerful anti-inflammatory effects on specific mediators or signaling pathways. It will require both a keen understanding of the mechanisms of action of such agents and the careful selection of ASD patients suitable for each treatment. This review will attempt to summarize the use of anti-inflammatory agents already used in targeting ASD patients, and then emerging anti-inflammatory measures applicable for ASD subjects based on scientific rationale and clinical trial data, if available. In our experience, some ASD patients were treated under diagnoses of autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. However, there are little clinical trial data specifically for ASD subjects. Therefore, these emerging immunomodulating agents for potential use for ASD subjects will be discussed based on preclinical data, case reports, or data generated in patients with other medical conditions. This review will hopefully highlight the expanding scope of immunomodulating agents for treating neuroinflammation in ASD subjects.

Maternal-fetal immunity and recurrent spontaneous abortion.

Recurrent Spontaneous Abortion (RSA) is a common pregnancy complication, that has multifactorial causes, and currently, 40%-50% of cases remain unexplained, referred to as Unexplained RSA (URSA). Due to the elusive etiology and mechanisms, clinical management is exceedingly challenging. In recent years, with the progress in reproductive immunology, a growing body of evidence suggests a relationship between URSA and maternal-fetal immunology, offering hope for the development of tailored treatment strategies. This article provides an immunological perspective on the pathogenesis, diagnosis, and treatment of RSA. On one hand, it comprehensively reviews the immunological mechanisms underlying RSA, including abnormalities in maternal-fetal interface immune tolerance, maternal-fetal interface immune cell function, gut microbiota-mediated immune dysregulation, and vaginal microbiota-mediated immune anomalies. On the other hand, it presents the diagnosis and existing treatment modalities for RSA. This article offers a clear knowledge framework for understanding RSA from an immunological standpoint. In conclusion, while the "layers of the veil" regarding immunological factors in RSA are gradually being unveiled, our current research may only scratch the surface. In terms of immunological etiology, effective diagnostic tools for RSA are currently lacking, and the efficacy and safety of immunotherapies, primarily based on lymphocyte immunotherapy and intravenous immunoglobulin, remain contentious.

Epitope Mapping of an Anti-Mouse CD39 Monoclonal Antibody Using PA Scanning and RIEDL Scanning.

A cell-surface ectonucleotidase CD39 mediates the conversion of extracellular adenosine triphosphate into immunosuppressive adenosine with another ectonucleotidase CD73. The elevated adenosine in the tumor microenvironment attenuates antitumor immunity, which promotes tumor cell immunologic escape and progression. Anti-CD39 monoclonal antibodies (mAbs), which suppress the enzymatic activity, can be applied to antitumor therapy. Therefore, an understanding of the relationship between the inhibitory activity and epitope of mAbs is important. We previously established an anti-mouse CD39 (anti-mCD39) mAb, C39Mab-1 using the Cell-Based Immunization and Screening method. In this study, we determined the critical epitope of C39Mab-1 using flow cytometry. We performed the PA tag (12 amino acids [aa])-substituted analysis (named PA scanning) and RIEDL tag (5 aa)-substituted analysis (named RIEDL scanning) to determine the critical epitope of C39Mab-1 using flow cytometry. By the combination of PA scanning and RIEDL scanning, we identified the conformational epitope, spanning three segments of 275-279, 282-291, and 306-323 aa of mCD39. These analyses would contribute to the identification of the conformational epitope of membrane proteins.

Accurate and reproducible enumeration of CD4 T cell counts and Hemoglobin levels using a point of care system: Comparison with conventional laboratory based testing systems in a clinical reference laboratory in Cameroon.

Measurements of CD4 T cells and hemoglobin (Hb) are conventionally used to determine the immunological state and disease progression for HIV-infected patients. We obtained a small lightweight point-of-care device, the BD FACSPrestoTM in order to demonstrate its ability to deliver CD4 and Hb analysis in comparison with two larger clinical machines the BDFACSCantoTM analyzer and Sysmex XN 1000 haematology analyzer. The advantages of using the POC device include access to HIV patient data in remote and in resource limited settings. The analytical performance of the BD FACSPrestoTM, compared with the FACSCantoTM II flow cytometer and the Sysmex XN 1000 haematology analyzer was evaluated by testing 241 routine clinical specimens collected in EDTA tubes from patients attending the Immunology and Microbiology laboratory of Chantal BIYA International Reference Centre (Yaounde, Cameroon) between January and May 2016. The mean in absolute counts and percentage of CD4 T cells was 606 cells/mL and 25% respectively via the FACSPrestoTM, and 574 cells/mL and 24% respectively via the BD FACSCantoTM II. The mean concentration of Hb levels was 11.90 on the Sysmex XN 1000 and 11.45 via the BD FACSPrestoTM, A high correlation (R2 = 0.95, P < 0.001) of Hb level measurements was noted between the BD FACSPrestoTM and Sysmex XN 1000 hematology analyzer. Overall, a Bland-Altman plot of the differences between the two methods showed an excellent agreement for absolute and percentage CD4 counts and hemoglobin measurements between POC and conventional methods evaluated here. Furthermore, the study demonstrated the ease of use of the BD FACSPrestoTM POC technology in remote areas. The BD FACPrestoTM is a suitable tool for CD4 enumeration in resource-limited settings, specifically providing a deployable, reliable POC testing option. The BD FACSPrestoTM performed appropriately in comparison to the conventional reference standard technologies. The BD FACSPrestoTM, system provides accurate, reliable, precise CD4/%CD4/Hb results on venous blood sampling. The data showed good agreement between the BD FACSPrestoTM, BD FACSCantoTM II and Sysmex XN 1000 XN 1000 systems.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer’s disease prediction

BackgroundPatients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. MethodsIn this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). ResultsIndependent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). ConclusionsBlood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

Keeping pace with the progress of immunology

Keeping pace with the progress of immunology

Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis.

Systemic sclerosis is a connective tissue disease of unknown origin and with an unpredictable course, with both cutaneous and internal organ manifestations. Despite the enormous progress in rheumatology and clinical immunology, the background of this disease is largely unknown, and no specific therapy exists. The therapeutic approach aims to treat and preserve the function of internal organs, and this approach is commonly referred to as organ-based treatment. However, in modern times, data from other branches of medicine may offer insight into how to treat disease-related complications, making it possible to find new drugs to treat this disease. In this review, we present therapeutic options aiming to stop the progression of fibrotic processes, restore the aberrant immune response, stop improper signalling from proinflammatory cytokines, and halt the production of disease-related autoantibodies.

A metagenome-wide association study of HIV disease progression in HIV controllers

Some HIV controllers experience immunologic progression with CD4+ Tcell decline. We aimed to identify genetic factors associated with CD4+ Tcell lost in HIV controllers. A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No SNP or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual GWAS or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p= 0.005; OR= 1.70], rs59440261 [p= 0.003; OR= 1.78]), MICA (rs112243036 [p= 0.011; OR= 1.45]), and PSORS1C1 loci (rs3815087 [p= 0.017; OR= 1.39]) showed nominal association with this phenotype. Genetic factors associated with the long-term HIV controllers without risk of immunologic progression are those previously related to the overall HIV controller phenotype.

Different treatment strategies in patients with HBeAg-positive and negative chronic hepatitis B

Patients with HBeAg-positive and negative chronic hepatitis B (CHB) have different immunological states and disease progression. Hence, the previously recommended antiviral therapy strategies for the two are different. In recent years, the antiviral indications have gradually eased, and the treatment goal has began to pursue clinical cure, as experts and scholars have gradually attached importance to the potential risk of disease progression in hepatitis B patients. Antiviral treatment strategies are gradually becoming uniform for patients with HBeAg-positive and negative. However, among them, HBeAg-negative patients can be combined with HBsAg quantification and other indicators to further screen the clinically cured dominant population in order to formulate the next treatment strategy.

Neuroimmunological renal function for zinc(Ⅱ) induced CKD prevention and modulatory progression

Zinc (Ⅱ) supplementation (30 mg/day) should become likely therapeutic chronic kidney disease (CKD) prevention implications with immense importance of CKD-associated immunological and neurological complications of central nervous system (CNS) disorder and peripheral nervous system (PNS) condition. Zinc induced neuro immunological inhibitive CKD progression with Stage 2～3A, 3B, zinc supplementation may be beneficial for nutritional status in CKD children and adolescents, and zinc could reduce urinary protein excretion composed of albumin and/or minimize proteinuria excretion in proteinuric CKD. In CKD 4～5 stage, risk of cardiovascular disease (CVD) become higher that zinc supplementation of 25 mg/day in zinc homeostasis has a beneficial effect for CVD in vascular dysfunction, in which zinc induced CKD Stage 5 (eGFR < 15) is involved that zinc is actively bound to several proteins that the decrease of circulating zinc levels in CKD is becoming zinc-deficiency with advanced stage CKD and ESRD in CKD. Zinc 15 mg/day and Selenium 50–70 μg/day that are recommended may be thought to prevent ESRD stage. Zinc induced NAD (P)H oxidase (Nox) activation occurring ROS generation in CKD cell involves assembly that ROS include the superoxide anion (O2•–), hydrogen peroxide (H2O2), and hydroxyl radicals (OH•) in the kidney. Zinc(Ⅱ) ions-binding protein molecular mechanism is involved that Zn2+ ions induced binding ligands of such as albumin, a-macroglobulin and transferrin in several proteins had been found on the binding specificity by Zn2+ ions-centered tetrahedral geometric coordination, in which causing zinc-activated serine, histidine and aspartate hydrogen residues enhance renal function activity and resulting inhibition of CKD progression proceeds.

Neuroimmune Crosstalk in Rheumatoid Arthritis.

Recent studies have demonstrated that immunological disease progression is closely related to abnormal function of the central nervous system (CNS). Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis-based systemic immune disease of unknown etiology. In addition to joint pathological damage, RA has been linked to neuropsychiatric comorbidities, including depression, schizophrenia, and anxiety, increasing the risk of neurodegenerative diseases in life. Immune cells and their secreted immune factors will stimulate the peripheral and central neuronal systems that regulate innate and adaptive immunity. The understanding of autoimmune diseases has largely advanced insights into the molecular mechanisms of neuroimmune interaction. Here, we review our current understanding of CNS comorbidities and potential physiological mechanisms in patients with RA, with a focus on the complex and diverse regulation of mood and distinct patterns of peripheral immune activation in patients with rheumatoid arthritis. And in our review, we also discussed the role that has been played by peripheral neurons and CNS in terms of neuron mechanisms in RA immune challenges, and the related neuron-immune crosstalk.

On the Flame: The Fab Fragment of Rheumatoid Arthritis

With more than 200,000 cases per year, Rheumatoid Arthritis (RA) is one of the most common autoimmune disorders in the United States. Across the globe, up to 14 million people are affected by its symptoms of joint pain, stiffness, swelling, fatigue, and even physical deformity. Rheumatoid factors (RF) are autoantibodies that correlate with RA severity and recognize epitopes in the Fc region of its antigen immunoglobulin (Ig) G, yet it is paradoxically found circulating in the blood alongside the antigen without binding to it. According to Thomsen, et. al, a 2018 study that contested the idea of IgG aggravation as the prerequisite to RF binding, the native state of IgG is present in a closed form, where the Fab fragment shields the Fc region, only exposing the Fc effector sites when a conformational change is induced. This closed form is a result of a missing galactose between the C□2 domains of the heavy chains, thus causing the IgG to self associate, forming immune complexes to fix the complement system. The subsequent heightened inflammatory response exacerbates the progression of joint damage in RA and other severe symptoms. In this study, we examined RF in relation to IgG forming immune complexes to achieve a better understanding of the immunological progression or pathogenesis of RA. The Mahtomedi MSOE Center for BioMolecular Modeling MAPS Team used 3‐D modeling and printing technology to examine structure‐function relationships of Fab and Fc fragments in IgG. The visual model will be a valuable tool in developing our story.

Probabilistically certified region of attraction of a tumor growth model with combined chemo‐ and immunotherapy

AbstractThe recent progress in immunology lead to a considerable interest in modeling cancer dynamics in order to better understand and analyze such complex systems. Many works have been carried out in order to design cancer treatment protocols using mathematical models. One of the main complexities of such models is the presence of different types of uncertainties, which remains less considered in the literature. This article deals with the estimation of regions of attraction (RoAs) under parametric uncertainties for a cancer growth model with combined therapies. We propose a framework of probabilistic certification, based on the randomized methods, in order to derive probabilistically certified RoAs of a cancer growth model. The model considered in this article describes the interaction between a tumor and the immune system in presence of a combined chemo‐ and immunotherapy treatment, with considerations on pharmacokinetics and pharmacodynamics of both treatments.

CXCR6-based immunotherapy in autoimmune, cancer and inflammatory infliction

T cells, including both CD4+ and CD8+ T cells, play a pivotal role in mediating various inflammation and immune disorders. A long-standing challenge in T cell-based immunotherapy is to precisely inactivate or delete the pathogenic T cells in inflammation and autoimmune diseases, or to selectively expand the immunocompetent T cell in tumor or other immune compromised situations, without inducing global immunosuppression or zealous immune activation respectively. To achieve this, a specific marker is needed to differentiate the pathogenic or immunocompetent T cell among the rests. Indeed, recent progress of immunology strongly suggests that CXC chemokine receptor 6 (CXCR6, CD186) is such a kind of marker. Here, we review the emerging role of CXCR6 as a novel target for immunotherapy and discuss the underlying mechanism. We propose that CXCR6-based immunotherapy will play a significant role in autoimmune, nonalcoholic steatohepatitis (NASH), tumor, coronavirus disease 2019 (COVID-19) and even ageing-related inflammatory infliction.

Prophylactic vaccines against cancers of non-infectious origin: a dream or a real possibility?

The dramatic progress in tumour biology and immunology in the past several years has opened new avenues for the treatment and prevention of cancer. One of the great contributions of the immunotherapeutic approaches is an increasing understanding of the immunology of cancer, which is, gradually creating conditions for the development of prophylactic anti-cancer vaccines. Efficient vaccines have been developed and employed for the prophylaxis of two frequent cancers of viral origin, namely cervical cancer and liver cancer. The new knowledge on the interactions between the immune system and the malignant tumors seems to provide means for the development of prophylactic vaccines against cancers developing due to the mutations in the proto-oncogenes converting their products into oncoproteins. According to the present estimates, these cancers form a great majority of human malignancies. Recent evidence has indicated that the immune system recognizes such mutated proteins, and that the development of cancer is due to the failure of the immune system to eliminate neoplastic cells. Followingly, it can be expected that inducing immunity against the mutated epitopes will increase the capacity of the body to deal with the initiated precancerous cells. In the present paper this hypothesis is primarily discussed in the relationship with colorectal cancer (CRC), which seems to be a well-fitting candidate for prophylactic vaccination. CRC is the third most frequent malignancy and the fourth most common cause of cancer mortality. Mutations of two proto-oncogenes, namely RAS and RAF, are involved in the majority of CRC cases and, in addition, they are shared with other human malignancies. Therefore, the strategy to be used for prophylaxis of CRC is discussed together with several other frequent human cancers, namely lung cancer, pancreatic duct cancer and melanoma. The prophylactic vaccines proposed are aimed at the reduction of the incidence of these and, to a lesser extent, some other cancers.

O25 Catastrophic antiphospholipid crisis triggered by anticoagulant switch

O25 Catastrophic antiphospholipid crisis triggered by anticoagulant switch