Immune Targets Research Articles

An Integrated Approach Utilizing Single-Cell and Bulk RNA-Sequencing for the Identification of a Mitophagy-Associated Genes Signature: Implications for Prognostication and Therapeutic Stratification in Prostate Cancer

Introduction: Prostate cancer, notably prostate adenocarcinoma (PARD), has high incidence and mortality rates. Although typically resistant to immunotherapy, recent studies have found immune targets for prostate cancer. Stratifying patients by molecular subtypes may identify those who could benefit from immunotherapy. Methods: We used single-cell and bulk RNA sequencing data from GEO and TCGA databases. We characterized the tumor microenvironment at the single-cell level, analyzing cell interactions and identifying fibroblasts linked to mitophagy. Target genes were narrowed down at the bulk transcriptome level to construct a PARD prognosis prediction nomogram. Unsupervised consensus clustering classified PARD into subtypes, analyzing differences in clinical features, immune infiltration, and immunotherapy. Furthermore, the cellular functions of the genes of interest were verified in vitro. Results: We identified ten cell types and 160 mitophagy-related single-cell differentially expressed genes (MR-scDEGs). Strong interactions were observed between fibroblasts, endothelial cells, CD8+ T cells, and NK cells. Fibroblasts linked to mitophagy were divided into six subtypes. Intersection of DEGs from three bulk datasets with MR-scDEGs identified 26 key genes clustered into two subgroups. COX regression analysis identified seven prognostic key genes, enabling a prognostic nomogram model. High and low-risk groups showed significant differences in clinical features, immune infiltration, immunotherapy, and drug sensitivity. In prostate cancer cell lines, CAV1, PALLD, and ITGB8 are upregulated, while CLDN7 is downregulated. Knockdown of PALLD significantly inhibits the proliferation and colony-forming ability of PC3 and DU145 cells, suggesting the important roles of this gene in prostate cancer progression. Conclusions: This study analyzed mitophagy-related genes in PARD, predicting prognosis and aiding in subtype identification and immunotherapy response analysis. This approach offers new strategies for treating prostate cancer with specific molecular subtypes and helps develop potential biomarkers for personalized medicine strategies.

Host-Directed Therapy with Inhalable Lovastatin Microspheres for Matrix Metalloproteinase Inhibition in Tuberculosis.

Tuberculosis (TB) triggers a robust immune response, which leads to significant destruction of the lung tissue at the site of infection, aiding in the transmission of Mycobacterium tuberculosis (Mtb) to the hosts. The excessive inflammatory response contributes heavily to extracellular matrix (ECM) damage, which is linked to high mortality rates among TB patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are pivotal in the breakdown of the ECM, worsening tissue destruction. In the context of host-directed therapy (HDT), a strategy aimed at modulating the immune response rather than directly targeting the pathogen, we evaluated the potential of lovastatin (LOV). LOV has shown promise in reducing MMP activity and inflammation, which could alleviate the immune-mediated pathology in TB. However, its clinical use has been limited due to poor solubility and biocompatibility, reducing its therapeutic efficacy. To overcome these limitations, we designed inhalable gelatin microspheres (GA-MS) loaded with LOV using the spray-drying technology. This approach improved the solubility and allowed for the controlled release of the drug. The resulting LOV-loaded gelatin microspheres (LOV/GA-MS) had an optimal particle size of 2.395 ± 0.67 μm, facilitating macrophage uptake due to their aerodynamic properties. In in vitro studies using Mtb-infected macrophages, LOV/GA-MS effectively suppressed MMP expression and reduced levels of pro-inflammatory cytokines at a concentration of 20 μg/mL, demonstrating substantial anti-inflammatory potential. Moreover, these microspheres showed a synergistic effect when combined with standard anti-TB drugs, enhancing the overall therapeutic efficacy in in vitro experiments. The findings suggest that inhalable LOV/GA-MS microspheres represent a promising adjunctive host-directed therapy for TB. By modulating the host's immune response and targeting key inflammatory mediators such as MMPs, this approach could mitigate lung tissue damage, improve clinical outcomes, and provide a more holistic treatment option for TB.

Toxicity Associated with Pembrolizumab Monotherapy in Patients with Gastrointestinal Cancers: A Systematic Review of Clinical Trials.

Background/Objectives: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is a widely employed therapy for various gastrointestinal (GI) cancers. We conducted a systematic review of clinical trials investigating pembrolizumab monotherapy in GI cancer patients to assess the spectrum and incidence of immune-related adverse events (irAEs) associated with pembrolizumab. Methods: A comprehensive search of PubMed/MEDLINE was performed to identify clinical trials investigating pembrolizumab monotherapy in GI cancer patients. Primary endpoints included the incidence of grade 3 or higher irAEs and the rate of treatment discontinuation due to irAEs. Secondary endpoints encompassed the incidence of any-grade irAEs, as well as specific irAEs. Results: Data extraction and analysis were performed on 25 articles. The analysis included 3101 patients with a median age of 62 years (range 53-68), with 30.2% being female. Tumor types encompassed were colorectal (12%), esophagogastric (46%), hepatocellular carcinoma (24%), and other GI tumor types (18%). The rate of treatment discontinuation due to irAEs was 6.8%. The most prevalent grade 3 or higher irAEs were hepatitis (3.6%), pneumonitis (0.8%), and colitis (0.7%). Death attributed to irAEs was infrequent (0.9%). Conclusions: In patients with GI cancers treated with pembrolizumab monotherapy, severe toxicities are infrequent, and irAEs leading to treatment discontinuation or death are uncommon.

PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells

BackgroundPRDX2 is significantly expressed in various cancers and is associated with the proliferation of tumor cells. Nonetheless, the precise mechanism of PRDX2 in tumor immunity remains incompletely understood. This study aims to investigate the impact of PRDX2, which is highly expressed in lung adenocarcinoma, on T cells in the tumor immune microenvironment, and its immune action target to promote the immune escape of lung cancer cells, to provide a theoretical basis for lung adenocarcinoma treatment with PRDX2 as the target.MethodsMouse animal models to verify the effect of Conoidin A treatment on tumor growth and T cell infiltration. Flow cytometry and Western blot verified tumor cell apoptosis in the in vitro co-culture system as well as granzyme B and perforin expression in T cells. RNA-Seq was used to obtain the downstream immune molecule. si-RNA knockdown of Galectin-9 was co-cultured with T cells in vitro. Immunofluorescence and Western blot verified that PRDX2 regulates Galectin-9 expression through HDAC3.ResultsPRDX2 expression was negatively correlated with CD8+ T cell expression in LUAD patients. Inhibition of PRDX2 significantly enhanced T-cell killing of LUAD cells and reduced tumor load in both in vitro and in vivo models. Mechanistically, Conoidin A or shRNA_PRDX2 decreased Galectin-9 expression by down-regulating the phosphorylation of HDAC3, consequently enhancing the infiltration and function of CD8+ T cells.ConclusionsThis study reveals the role of the PRDX2/HDAC3/Galectin-9 axis in LUAD immune escape and indicates Galectin-9 as a promising target for immunotherapy.

Ocular Rosacea: An Updated Review.

Ocular rosacea is a chronic inflammatory disorder affecting the ocular surface, often associated with cutaneous rosacea. This review aims to explore its pathogenesis, treatment approaches, and future directions for management. A review of current literature on the pathophysiology, clinical features, and treatment strategies of ocular rosacea in adults and children (pediatric blepharokeratoconjunctivitis) was conducted. Emerging research on immune dysregulation, microbiome alterations, and potential therapeutic targets was analyzed. Ocular rosacea involves dysregulation of the immune and neurovascular systems, with toll-like receptor activation and complement system involvement leading to chronic ocular surface inflammation. Alterations in the ocular microbiome have been implicated in disease progression. Treatment strategies emphasize a stepwise approach, incorporating ocular and skin hygiene, lifestyle modifications, and pharmacological interventions. Recent advancements in understanding the disease mechanisms have led to the exploration of targeted therapies, including biologics and small-molecule inhibitors. Ocular rosacea remains challenging to diagnose and treat, particularly in children (pediatric blepharokeratoconjunctivitis), often leading to delayed intervention and poor outcomes. A multidisciplinary approach, including new therapeutic options, holds promise for improving patient care. Further research into the genetic and molecular basis of ocular rosacea may enable more personalized treatments.

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5.

People living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), even though combination antiretroviral therapy (cART) suppresses HIV replication. HIV-1 transactivator of transcription (HIV-1 Tat) contributes to the development of HAND through neuroinflammatory and neurotoxic mechanisms. C-C chemokine 5 receptor (CCR5) is important in immune cell targeting and is a co-receptor for HIV viral entry into CD4+ cells. Notably, CCR5 has been implicated in cognition unrelated to HIV infection. Inhibition of CCR5 has been shown to improve learning and memory. To test whether CCR5 is involved in cognitive changes in HAND, we used a non-infectious, transgenic model in which HIV-1 Tat is inducibly expressed. Well-powered cohorts of male and female mice were placed on a diet containing doxycycline to induce Tat expression for 8-wks. Males showed Tat-mediated deficits in the Barnes maze test of spatial learning and memory; females showed no impairments. Deficits in the males were fully reversed by the CCR5 antagonist, maraviroc (MVC). Tat-mediated deficits were not found in novel object recognition or contextual fear conditioning in either sex. Based on earlier work, we hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), which is essential in maintaining synaptodendritic function. MVC did increase the mBDNF to proBDNF ratio in males, perhaps contributing to improved cognition.

Illuminating the impact of CD38-induced adenosine formation in B-cell lymphoma

The expression of CD38 by cancer cells may mediate an immune-suppressive effect by producing Extracellular Adenosine (ADO) acting through G-protein-coupled cell surface receptors on cellular components and tumor cells. This can increase PD-1 expression and interaction with PD-L1, suppressing CD8 + cytotoxic T cells. This study examines the impact of heightened CD38 expression and extracellular ADO on various hematological and clinical parameters in patients with mature B-cell lymphoma, alongside their correlation with the soluble counterparts of the PD-1/PD-L1 axis. Our study was conducted on 90 patients, CD38-positive and CD38-negative (measured by flow cytometry), with mature B-cell lymphoma divided into CLL and B-NHL subtypes. Their serum ADO, soluble PD-1, and PD-L1 levels were measured using a sandwich ELISA. Our study revealed a positive correlation between CD38 expression, sADO, sPD-1, and sPD-L1 in mature B-cell lymphoma patients. CD38-positive patients had higher sADO, sPD-1, and sPD-L1 levels. Higher CD38 expression and extracellular ADO negatively affected HB level and PLT count and positively correlated with the higher risk stratification in mature B-cell lymphoma patients. This study explored the potential impact of CD38 expression and elevated extracellular ADO on B-cell lymphoma alongside their link with the PD-1/PD-L1 axis. Our findings underscore the influence of extracellular ADO on the neoplastic process of mature B-cell lymphoma. We also propose targeting the CD38-induced-ADO formation pathway, which could serve as a promising therapeutic immune target with multifaceted effects within mature B-cell neoplasms.

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes and tumor suppressor genes in transformed cells, significantly contributes to tumor development at both primary and distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues and downstream signals, altering the phenotype of stromal cells and immune cells. This remolds the area surrounding tumor cells, ultimately fostering an immunosuppressive microenvironment. Therefore, correcting the TME by targeting the epigenetic modifications holds substantial promise for cancer treatment. This review synthesizes recent research that elucidates the impact of specific epigenetic regulations-ranging from DNA methylation to histone modifications and chromatin remodeling-on stromal and immune cells within the TME. Notably, we highlight their functional roles in either promoting or restricting tumor progression. We also discuss the potential applications of epigenetic agents for cancer treatment, envisaging their ability to normalize the ecosystem. This review aims to assist researchers in understanding the dynamic interplay between epigenetics and the TME, paving the way for better epigenetic therapy.

Immunomodulatory insights of monoterpene glycosides in endometriosis: immune infiltration and target pathways analysis

Endometriosis is a complex gynecological condition characterized by abnormal immune responses. This study aims to explore the immunomodulatory effects of monoterpene glycosides from Paeonia lactiflora on endometriosis. Using the ssGSEA algorithm, we assessed immune cell infiltration levels between normal and endometriosis groups. Key targets were identified through differential expression analysis of the GSE51981 dataset. Potential immunomodulatory targets of Paeonia lactiflora compounds were identified through Venn diagram analysis, followed by enrichment and machine learning analyses. A nomogram was developed for predicting endometriosis, while molecular docking explored compound-target interactions. Significant differences in immune cell infiltration were observed, with increased CD8 T cells, cytotoxic cells, and others in endometriosis. Differential expression analysis identified 43 potential targets. Enrichment analysis highlighted pathways involved in immune and inflammatory responses. Machine learning identified SSTR5, CASP3, FABP2, and SYK as critical targets, contributing to a nomogram that demonstrated good predictive performance for endometriosis risk. Molecular docking revealed strong interactions between Paeoniflorigenone and CASP3. Our findings suggest that monoterpene glycosides have therapeutic effects on endometriosis by modulating key immune-related targets and pathways, providing a basis for further investigation into Paeonia lactiflora’s potential as a treatment for this condition.

Immune targets for schistosomiasis control identified by a genome-wide association study of African snail vectors.

Schistosomiasis, a neglected tropical disease, is transmitted by freshwater snails. Interruption of transmission will require novel vector-focused interventions. We performed a genome-wide association study of African snails, Biomphalaria sudanica , exposed to Schistosoma mansoni in an endemic area of high transmission in Kenya. Two snail genomic regions, SudRes1 and SudRes2, were significantly associated with snail immunity to schistosomes. SudRes1 includes receptor-like protein tyrosine phosphatases while SudRes2 includes a class of leucine-rich repeat-containing G-protein coupled receptors, both comprising diverse extracellular binding domains suggestive of host-pathogen interaction. Resistant and susceptible haplotypes show numerous coding differences including presence/absence of entire genes. No loci previously tied to schistosome resistance in neotropical snail species showed any association with compatibility suggesting that loci involved in the resistance of African vectors are distinct. Snail ancestry was also strongly correlated with parasite compatibility. These results will inform future efforts to predict and manipulate immunity of a major schistosome vector.

Ultrasound-triggered drug-loaded nanobubbles for enhanced T cell recruitment in cancer chemoimmunotherapy.

Chemotherapy combined with immunotherapy is a highly promising approach for treating tumors. However, chemotherapeutic drugs often fail to accumulate effectively at the tumor site after systemic administration and they lack sufficient immunogenicity to activate adaptive immunity, making an effective T-cell immune response within the tumor microenvironmentdifficult to achieve. Here, this work developed drug-loaded nanobubbles (DTX-R837@NBs) that encapsulate the chemotherapy drug docetaxel and the immune adjuvant R837 via a thin-film hydration method. Ultrasound-targeted nanobubble destruction promoted drug accumulation within tumor tissues and damaged tumor cells through the cavitation effect, inducing immunogenic cell death and releasing damage-associated molecular patterns to augment dendritic cell maturation. Notably, DTX-R837@NBs exhibited excellent contrast-enhanced ultrasound imaging capabilities, enabling the seamless integration of diagnosis and treatment. In combination with immune checkpoint blockade targeting programmed cell death protein 1 (PD-1), the generated immunological responses attacked residual tumor cells and ameliorated the immunosuppressive tumor microenvironment, inhibiting distant tumor growth and metastasis. Moreover, this strategy exhibited robust immune memory effects, effectively protecting the host and preventing tumor recurrence upon rechallenge. Overall, ultrasound-mediated DTX-R837@NBs combined with anti-PD-1 immune checkpoint blockade therapy exhibits robust antitumor efficiency, represent a promising strategy for overcoming immunotherapy resistance in cold tumors, and warrant further investigation for clinical translation.

Discovery and exploration of adaptive immune response-related drug targets in diabetic retinopathy by Mendelian randomization

Discovery and exploration of adaptive immune response-related drug targets in diabetic retinopathy by Mendelian randomization

Immune Mechanisms and Treatment Targets in Rheumatoid Arthritis

Immune Mechanisms and Treatment Targets in Rheumatoid Arthritis

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Malaria is a complex parasitic disease caused by species of Plasmodium parasites. Infection with the parasites can lead to a spectrum of symptoms and disease severity, influenced by various parasite, host, and environmental factors. There have been some successes in developing vaccines against the disease recently, but the vaccine efficacies require improvement. Some issues associated with the difficulties in developing a sterile vaccine include high antigenic diversity, switching expression of the immune targets, and inhibition of immune pathways. Current vaccine research focuses on identifying conserved and protective epitopes, developing multivalent vaccines (including the whole parasite), and using more powerful adjuvants. However, overcoming the systematic immune inhibition and immune cell dysfunction/exhaustion may be required before high titers of protective antibodies can be achieved. Increased expression of surface molecules such as CD86 and MHC II on antigen-presenting cells and blocking immune checkpoint pathways (interactions of PD-1 and PD-L1; CTLA-4 and CD80) using small molecules could be a promising approach for enhancing vaccine efficacy. This assay reviews the factors affecting the disease severity, the genetics of host-parasite interaction, immune evasion mechanisms, and approaches potentially to improve host immune response for vaccine development.

Comprehensive analysis reveals PLK3 as a promising immune target and prognostic indicator in glioma.

PLK3, which played an important role in cell cycle progression and stress response, was identified as highly expressed in various carcinomas. However, the functions, molecular characteristics, and prognostic value of PLK3 in glioma remained unexplored. We analyzed PLK3 expression in glioma samples from multiple databases. Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma, and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression. Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration. The trans-well assay for PLK3 on the immune cells recruitment was also determined. Additionally, we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints. We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma, and further validated that PLK3 promoted glioma progression. PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression. Specifically, we revealed that CD8+ and CD4+ Tcell infiltration was decreased in Plk3 overexpressed xenografts. Furthermore, it was predicted that PLK3 was synergistic with other checkpoint members in glioma. In general, high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients. Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas, and we validated that PLK3 could promote the GBM progress in vitro and in vivo. Furthermore, PLK3 played important roles in Tcell and neutrophil immune response in glioma. Besides, the conspicuous association between PLK3 and other immune checkpoints was also observed. Crucially, high-level PLK3 expression was revealed to be related to poor clinical prognosis. These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.

Tissue Determinants of Antiviral Immunity in the Liver.

The liver is an organ bearing important metabolic and immune functions. Hepatocytes are the main metabolically active cells of the liver and are the target of infection by hepatotropic viruses. Virus-specific CD8 T cells are essential for the control of hepatocyte infection with hepatotropic viruses but may be subject to local regulation of their effector function. Here, we review our current knowledge of the tissue determinants of antiviral immunity in the liver. Liver Sinusoidal Endothelial Cells (LSECs) not only allow through their fenestrations the access of circulating virus-specific CD8 T cells to engage in direct contact with infected hepatocytes without the need for extravasation but also cross-present viral antigens released from infected hepatocytes to these CD8 T cells. Two important features of LSECs and hepatocytes contribute to antiviral immune surveillance and liver failure. First, CD8 T cell immunity targeting LSECs leads to widespread endothelial cell death and results in sinusoidal microcirculation failure, causing fulminant viral hepatitis, whereas immune-mediated loss of hepatocytes is rapidly compensated by the regenerative capacity of the liver. Second, virus-infected hepatocytes support clearance of infection by responding to TNF, which is released from virus-specific CD8 T cells, with the selective induction of apoptosis. This increased sensitivity for TNF-induced death is caused by reduced mitochondrial resilience in virus-infected hepatocytes and may assist antiviral immunity in preferential targeting of virus-infected hepatocytes. Thus, hepatocytes and LSECs actively contribute to the outcome of antiviral CD8 T cell immunity in the liver. The knowledge of the mechanisms determining CD8 T cell control of hepatotropic viral infection will help to improve strategies to increase antiviral immune surveillance.

A new strategy for drug delivery systems in oral diseases using stem cell-derived extracellular vesicles: review and new perspectives.

Extracellular vesicles (EVs) are membrane vesicles derived from cells and serve as an endogenous mechanism for intercellular communication. Since the discovery of their capacity to effectively transfer biological information, their potential as drug delivery vehicles has garnered significant scientific interest. Particularly, EVs derived from mesenchymal cells (MSC-EVs) have emerged as a highly promising method for drug delivery. They can transport bioactive molecules, such as nucleic acids, lipids, and proteins, and possess the ability to modulate immune responses, transmit information, and target specific cells. EVs offer several advantages over conventional drug delivery systems, including their capacity to traverse natural barriers, inherent cell targeting capabilities, and stability in circulation. Compared to their parent cells, EVs exhibit low immunogenicity, ease of storage and transport, and a reduced risk of tumorigenesis. The diagnosis and treatment of oral diseases often involve invasive measures, and MSC-EVs have demonstrated initial efficacy in oral disease treatment. This review explores the application of MSC-EVs in maxillofacial tissue regeneration, periodontitis, temporomandibular joint osteoarthritis, Sjögren's Syndrome, oral cancer, and other oral diseases. Additionally, it outlines potential future directions for the development of MSC-EVs. This review aims to provide a comprehensive understanding of MSC-EVs in oral disease treatment and to stimulate interest in their applications for targeted drug delivery.

Immune Checkpoint Inhibitors in Breast Cancer

The incidence of breast cancer has risen dramatically over the past few decades and has become the most common malignancy in women. By 2040, it is expected that there will be more than 3 million new cases of breast cancer and more than 1 million deaths per year. The incidence of breast cancer has risen dramatically over the past few decades and has become the most common malignancy in women. By 2040, it is expected that there will be more than 3 million new cases of breast cancer and more than 1 million deaths per year. Immune checkpoint therapeutics was significant technological breakthrough on cancer treatment programs. It uses the body’s immune system targets and eliminates cancer cells. This therapy maintains self-tolerance and modulates the immune response to minimize tissue damage during infection. This therapy inhibits immune checkpoints such as PD-1, PD-L1, and CTLA-4, which tumors exploit to evade immune detection. By blocking these pathways, immune checkpoint inhibitors can reactivate T cells, enabling them to recognize and attack breast cancer cells. This essay will explain how does checking for inhibitors help T cells recognize the breast tumor cells, and some drugs specialize in PD-1 and CTLA-4.

Vaccination as a Promising Approach in Cardiovascular Risk Mitigation: Are We Ready to Embrace a Vaccine Strategy?

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As atherosclerosis is marked by chronic arterial inflammation, the innate and adaptive immune systems play vital roles in its progression, either exacerbating or alleviating disease development. This intricate interplay positions the immune system as a compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none have yet reached widespread clinical adoption. Safety concerns, particularly the suppression of host immune defenses, remain a significant barrier to the clinical application of anti-inflammatory therapies. Recent decades have revealed the significant role of adaptive immune responses to plaque-associated autoantigens in atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related autoantigens can slow disease progression while preserving systemic immune function. In this context, numerous experimental studies have advanced the understanding of vaccine development by exploring diverse targeting pathways. Key strategies include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies and active immunization targeting low-density lipoprotein cholesterol (LDL-C) and apolipoproteins, such as apolipoprotein B100 (ApoB100) and apolipoprotein CIII (ApoCIII). Other approaches involve vaccine formulations aimed at proteins that regulate lipoprotein metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and angiopoietin-like protein 3 (ANGPTL3). Furthermore, the literature highlights the potential for developing non-lipid-related vaccines, with key targets including heat shock proteins (HSPs), interleukins (ILs), angiotensin III (Ang III), and a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe and effective clinical therapies presents substantial challenges. This review provides a critical evaluation of current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms of action, and discusses key challenges that need to be overcome to enable clinical translation.

Immunology and treatments of fatty liver disease.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are two major chronic liver diseases worldwide. The triggers for fatty liver can be derived from external sources such as adipose tissue, the gut, personal diet, and genetics, or internal sources, including immune cell responses, lipotoxicity, hepatocyte death, mitochondrial dysfunction, and extracellular vesicles. However, their pathogenesis varies to some extent. This review summarizes various immune mechanisms and therapeutic targets associated with these two types of fatty liver disease. It describes the gut-liver axis and adipose tissue-liver crosstalk, as well as the roles of different immune cells (both innate and adaptive immune cells) in fatty liver disease. Additionally, mitochondrial dysfunction, extracellular vesicles, microRNAs (miRNAs), and gastrointestinal hormones are also related to the pathogenesis of fatty liver. Understanding the pathogenesis of fatty liver and corresponding therapeutic strategies provides a new perspective for developing novel treatments for fatty liver disease.