Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.

The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.

Immune Implications of Cholesterol-Containing Lipid Nanoparticles.

The majority of clinically approved nanoparticle-mediated therapeutics are lipid nanoparticles (LNPs), and most of these LNPs are liposomes containing cholesterol. LNP formulations significantly alter the drug pharmacokinetics (PK) due to the propensity of nanoparticles for uptake by macrophages. In addition to readily engulfing LNPs, the high expression of cholesterol hydroxylases and reactive oxygen species (ROS) in macrophages suggests that they will readily produce oxysterols from LNP-associated cholesterol. Oxysterols are a heterogeneous group of cholesterol oxidation products that have potent immune modulatory effects. Oxysterols are implicated in the pathogenesis of atherosclerosis and certain malignancies; they have also been found in commercial liposome preparations. Yet, the in vivo metabolic fate of LNP-associated cholesterol remains unclear. We review herein the mechanisms of cellular uptake, trafficking, metabolism, and immune modulation of endogenous nanometer-sized cholesterol particles (i.e., lipoproteins) that are also relevant for cholesterol-containing nanoparticles. We believe that it would be imperative to better understand the in vivo metabolic fate of LNP-associated cholesterol and the immune implications for LNP-therapeutics. We highlight critical knowledge gaps that we believe need to be addressed in order to develop safer and more efficacious lipid nanoparticle delivery systems.

Transformable Gel-to-Nanovaccine Enhances Cancer Immunotherapy via Metronomic-Like Immunomodulation and Collagen-Mediated Paracortex Delivery.

The generation of non-exhausted effector T-cells depends on vaccine's spatiotemporal profile, and untimely delivery and low targeting to lymph node (LN) paracortex by standard bolus immunization show limited efficacy. By recapitulating the dynamic processes of acute infection, a bioadhesive immune niche domain (BIND) is developed that facilitates the delivery of timely-activating conjugated nanovaccine (t-CNV) in a metronomic-like manner and increased the accumulation and retention of TANNylated t-CNV (tannic acid coated t-CNV) in LN by specifically binding to collagen in subcapsular sinus where they gradually transformed into TANNylated antigen-adjuvant conjugate by proteolysis, inducing their penetration into paracortex through the collagen-binding in LN conduit and evoking durable antigen-specific CD8+ T-cell responses. The BIND combined with t-CNV, mRNA vaccine, IL-2, and anti-PD-1 antibody also significantly enhanced cancer immunotherapy by the dynamic modulation of immunological landscape of tumor microenvironment. The results provide material design strategy for dynamic immunomodulation that can potentiate non-exhausted T-cell-based immunotherapy.

Impact of gut microbiota on metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma: pathways, diagnostic opportunities and therapeutic advances.

Metabolic dysfunction-associated steatohepatitis (MASH) and progression to hepatocellular carcinoma (HCC) exhibits distinct molecular and immune characteristics. These traits are influenced by multiple factors, including the gut microbiome, which interacts with the liver through the "gut-liver axis". This bidirectional relationship between the gut and its microbiota and the liver plays a key role in driving various liver diseases, with microbial metabolites and immune responses being central to these processes. Our review consolidates the latest research on how gut microbiota contributes to MASH development and its progression to HCC, emphasizing new diagnostic and therapeutic possibilities. We performed a comprehensive literature review across PubMed/MedLine, Scopus, and Web of Science from January 2000 to August 2024, focusing on both preclinical and clinical studies that investigate the gut microbiota's roles in MASH and HCC. This includes research on pathogenesis, as well as diagnostic and therapeutic advancements related to the gut microbiota. This evidence emphasizes the critical role of the gut microbiome in the pathogenesis of MASH and HCC, highlighting the need for further clinical studies and trials. This is to refine diagnostic techniques and develop targeted therapies that exploit the microbiome's capabilities, aiming to enhance patient care in liver diseases.

Cytokine-armed vaccinia virus promotes cytotoxicity toward pancreatic carcinoma cells via activation of human intermediary CD56dimCD16dim natural killer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-reserve vaccinia viruses (vvDD-IL2 and vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection were measured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine-armed virus targets the carcinoma cells and thus has great potential to modulate the TIME in PDAC.

The Immune Modulation HLA-G*01:01:01 Full Allele Is Associated with Gastric Adenocarcinoma Development.

The Human Leukocyte Antigen (HLA) system contains a set of genes involved at many levels in the innate and adaptive immune response. Among the non-classical HLA class I genes, HLA-G stands out for the numerous studies about its pivotal role in regulating/modulating immune responses. Also, its involvement in extravillous cytotrophoblast function, viral infections, autoimmunity, and cancer has been extensively documented. The present study explores for the first time the relationship between natural alleles of HLA-G, rather than STSs, SNPs, or partial gene polymorphisms, and the development of gastric adenocarcinoma, by analyzing the genetic profile of a cohort of 40 Spanish patients with this type of tumor using DNA extracted from paired biopsies of tumoral and adjacent non-tumoral gastric tissue. Our results reveal a significant statistical relationship between the presence of the HLA-G*01:01:01 allele and the development of gastric cancer, while other common alleles such as -G*01:04 or -G*01:05N did not demonstrate a significant correlation. Studying the involvement of HLA genes in the development of many diseases is relevant to understanding their pathophysiology. However, the absence of specific mechanisms underlying these associations suggests that investigating complete HLA natural alleles' extended haplotypes or complotypes may offer a more precise and valuable approach to elucidating the association of HLA with the pathogenesis of disease.

The emerging roles of microbiome and short-chain fatty acids in the pathogenesis of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants and leads to long-term pulmonary complications. The pathogenesis of BPD has not been fully elucidated yet. In recent years, the microbiome and its metabolites, especially short-chain fatty acids (SCFAs), in the gut and lungs have been demonstrated to be involved in the development and progression of the disease. This review aims to summarize the current knowledge on the potential involvement of the microbiome and SCFAs, especially the latter, in the development and progression of BPD. First, we introduce the gut-lung axis, the production and functions of SCFAs, and the role of SCFAs in lung health and diseases. We then discuss the evidence supporting the involvement of the microbiome and SCFAs in BPD. Finally, we elaborate on the potential mechanisms of the microbiome and SCFAs in BPD, including immune modulation, epigenetic regulation, enhancement of barrier function, and modulation of surfactant production and the gut microbiome. This review could advance our understanding of the microbiome and SCFAs in the pathogenesis of BPD, which also helps identify new therapeutic targets and facilitate new drug development.

Monoclonal antibodies in phase II and III trials for moderate to severe atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease that significantly affects quality of life and mental health, especially in children. Traditional treatments include chemotherapeutics, topical corticosteroids, and immunomodulatory agents, but recent advances have introduced novel monoclonal antibody therapies. Through this comprehensive review paper, we aim to discuss these therapeutic options and their role in treating atopic dermatitis. AREAS COVERED: A comprehensive search of the NIH Clinical Trials database was conducted from September 2023 to January 2024, focusing on phase 2 and 3 trials for AD treatments. Trials were filtered using keywords such as 'atopic dermatitis,' 'monoclonal antibody,' and 'phase 2/3.' Out of 25 trials analyzed, 11 were in phase 2 and 14 in phase 3. Only U.S.-based trials comparing novel therapies to placebo were included. In addition to the clinical trial database, we utilized the companies' websites and relevant abstracts to gather the latest results. EXPERT OPINION: Currently investigated monoclonal antibodies have the ability to transform management by targeting specific mediators implicated in the inflammatory pathway of AD. The results of Phase II and III trials for monoclonal antibodies demonstrated strong therapeutic potential with significant reductions in EASI scores and represent a promising new targeted treatment option.

Tumor microenvironment as a complex milieu driving cancer progression: a mini review.

It has been spotlighted that the Tumor Microenvironment (TME) is crucial for comprehending cancer progression and therapeutic resistance. Therefore, this comprehensive review elucidates the intricate architecture of the TME, which encompasses tumor cells, immune components, support cells, and a myriad of bioactive molecules. These constituents collectively foster dynamic interactions that underpin tumor growth, metastasis, and nuanced responses to anticancer therapies. Notably, the TME's role extends beyond mere physical support, serving as a critical mediator in cancer-cell evolution, immune modulation, and treatment outcomes. Innovations targeting the TME, including strategies focused on the vasculature, immune checkpoints, and T-cell therapies, have forged new pathways for clinical intervention. However, the heterogeneity and complexity of the TME present significant challenges, necessitating deeper exploration of its components and their interplay to enhance therapeutic efficacy. This review underscores the imperative for integrated research strategies that amalgamate insights from tumor biology, immunology, and systems biology. Such an approach aims to refine cancer treatments and improve patient prognoses by exploiting the TME's complexity.

Light-Driven Green-Fabricated Artificial Intelligence-Enabled Micro/Nanorobots for Multimodal Phototherapeutic Management of Bladder Cancer.

Combination therapy based on precise phototherapies combined with immune modulation provides successful antitumor effects. In this study, a combination therapy is designed based on phototactic, photosynthetic, and phototherapeutic Chlamydomonas Reinhardtii (CHL)-glycol chitosan (GCS)-polypyrrole (PPy) nanoparticle (NP)-enhanced immunity combined with the tumor microenvironment turnover of cytotoxic T cells and M1/M2 macrophages, which is based on photothermal GCS-PPy NPs decorated onto the phototactic and photosynthetic CHL. Phototherapy based on CHL-GCS-PPy NPs alleviates hypoxia and modulates the tumor immune microenvironment, which induces tumor cell death. In particular, the precise antitumor immune response and potent immune memory induced by combining self-navigated phototherapies significantly alleviate the progression of bladder cancer in C57BL/6 mice and effectively inhibit bladder tumor growth. Furthermore, they also potentially prevent tumor recurrence, which provides a promising therapeutic strategy for clinical tumor therapy.

Dose Considerations for Vaccinia Oncolytic Virus Based on Retrospective Reanalysis of Early and Late Clinical Trials.

Over the past decade, oncolytic viruses (OVs) have been developed as a promising treatment alone or in combination in immuno-oncology but have faced challenges in late-stage clinical trials. Our retrospective reanalysis of vaccinia oncolytic virus (VOV) clinical trials indicates that lower doses-rather than the maximum tolerated dose (MTD)-are associated with better tumor response rates. Patients who responded well to lower doses generally had prolonged survival rates in the early phase clinical trial. The association between poor outcomes and an increase in OV-induced neutrophils (OV-N) but not baseline neutrophil counts suggests the need for a comprehensive characterization of OV-N. Although this reanalysis is limited by patient heterogeneity-including differences in cancer type and stage, treatment schedules, and administration routes-it remains informative given the complexities of translational studies in the tumor-bearing mouse models of vaccinia oncolytic viruses. Notably, while OV-N increases with higher viral doses, the immune state shaped by tumor progression likely amplifies this tendency. These findings highlight the importance of OV-N immune modulation as well as dose optimization for the successful clinical development of VOV.

Substance P alleviates liver fibrosis by modulating inflammation and mobilizing reparative stem cells.

Repetitive hepatic damage resulting from viral hepatitis, toxins, and alcohol abuse induces chronic inflammation and excessive accumulation of the extracellular matrix, leading to the development of liver cirrhosis. Substance P (SP) promotes endogenous wound healing by mobilizing bone marrow stem cells and stimulating anti-inflammatory responses. This study aimed to investigate whether SP exerts a therapeutic effect on liver fibrosis by recruiting endogenous stem cells and modulating immune responses. A non-clinical model of liver cirrhosis was established through repeated injections of thioacetamide and recombinant leptin. After confirming liver fibrosis, SP was administered intravenously for 6 weeks. SP treatment decreased the formation of hepatic micronodules on the external surface of the liver and the infiltration of immune cells. Furthermore, SP treatment notably reduced the deposition of collagen and the activation of hepatic stellate cells, concomitant with decreased levels of transforming growth factor-ß1 and matrix metalloproteinase activity. In the context of severe hepatic damage, SP increased the number of circulating stem cells, leading to the restoration of the reparative stem cell pool in the bone marrow. The findings of this study suggest that SP alleviates liver fibrosis by modulating the mobilization of functional stem cells and the immune response.

Conferring alloantigen specificity to regulatory T cells: A comparative analysis of cell preparations undergoing clinical development in transplantation.

Conferring alloantigen-specificity to ex vivo expanded CD4+CD25+FOXP3+ regulatory T cells (Tregs) increases their capacity to counteract effector alloimmune responses following adoptive transfer into transplant recipients. Three strategies are currently undergoing clinical development, which involve the following: (1) expanding Tregs in the presence of donor B cells (donor alloantigen-reactive [DAR] Tregs); (2) culturing Tregs with donor cells in the presence of costimulation blockade (CSB-Tregs); and (3) transducing Tregs with an human leukocyte antigen A2-specific chimeric antigen receptor (CAR-Tregs). Our goal in this study was to assess the relative potency of each of these manufactured Treg products both in vitro and in vivo. When compared with polyclonal Tregs, all 3 manufacturing strategies increased the precursor frequency of alloreactive Tregs, and this was proportional to the overall in vitro immunosuppressive properties of the cell products. Accordingly, CAR-Tregs, which contained the highest frequency of donor-reactive Tregs, exhibited the strongest suppressive effects on a cell-per-cell basis. Similarly, in an in vivo mouse model of graft-vs-host disease, infusion of CAR-Tregs conferred a significantly longer recipient survival than any other Treg product. Our results highlighting the alloantigen-reactivity and associated immunosuppressive properties of different manufactured Treg products have implications for the mechanistic interpretation of currently ongoing clinical trials in transplantation.

The brain-heart-immune axis: a vago-centric framework for predicting and enhancing resilient recovery in older surgery patients.

Nearly all geriatric surgical complications are studied in the context of a single organ system, e.g., cardiac complications and the heart; delirium and the brain; infections and the immune system. Yet, we know that advanced age, physiological stress, and infection all increase sympathetic and decrease parasympathetic nervous system function. Parasympathetic function is mediated through the vagus nerve, which connects the heart, brain, and immune system to form, what we have termed, the brain-heart-immune axis. We hypothesize that this brain-heart-immune axis plays a critical role in surgical recovery among older adults. In particular, we hypothesize that the brain-heart-immune axis plays a critical role in the most common surgical complication among older adults: postoperative delirium. Further, we present heart rate variability as a measure that may eventually become a multi-system vital sign evaluating brain-heart-immune axis function. Finally, we suggest the brain-heart-immune axis as a potential interventional target for bio-electronic neuro-immune modulation to enhance resilient surgical recovery among older adults.

Relationship between urinary tract infections and serum vitamin D level in adults and children- a literature review.

Over time, researchers have accumulated significant evidence indicating that vitamin D deficiency not only impacts skeletal health but also contributes to the development and progression of various diseases, including cancer, diabetes, and cardiovascular conditions. The risk of low serum 1, 25(OH)2D3 level ultimately directs the way to morbidity, the beginning of new diseases, and numerous infections. Infections are the first entity that affects those with vitamin D deficiency. The common infection is urinary tract infection (UTI), and its relationship with vitamin D deficiency or insufficiency remains controversial. This infection affects both men and women, but comparatively, women are more prone to this infection because of the short length of the urethra, which makes an easy entry for the bacteria. The low level of serum vitamin D increases the risk of UTIs in children. Recurrent UTIs are one of the major weaknesses in women; if left untreated, they progress to appallingly serious conditions like kidney dysfunction, liver damage, etc. Hence improving the vitamin D status may help to improve the immune system, thus making it more resistant to infections. In this review, we have focused on examining whether vitamin D deficiency and insufficiency are the causes of UTIs and the association between them in women and children. We have also described the connection between vitamin D deficiency and insufficiency with UTIs and additional nanotechnology- based treatment strategies.

The Role of Vitamin D in Hematopoietic Stem Cell Transplantation: Implications for Graft-versus-Host Disease-A Narrative Review.

INTRODUCTION/AIM: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients. METHODS: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases. RESULTS: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed. CONCLUSION: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT.

Influence of Anesthetic Techniques on Colorectal Cancer Recurrence: A Comprehensive Review.

Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide, with a significant risk of recurrence following surgical treatment. Emerging evidence suggests that perioperative factors, particularly anesthetic techniques, may influence cancer recurrence rates. This comprehensive review aims to critically analyze the impact of various anesthetic techniques on colorectal cancer recurrence. We explore the distinct immunomodulatory and inflammatory effects of general, regional, and combined anesthetic approaches and their potential influence on tumor biology. The review synthesizes findings from clinical studies, experimental research, and theoretical models, highlighting the differential impact of anesthetic choices on long-term oncological outcomes. By examining recurrence rates, immune responses, and inflammatory markers associated with different anesthetic techniques, this review provides a holistic understanding of the role of anesthetic management in colorectal cancer surgery. Our findings suggest that anesthetic techniques can modulate the immune and inflammatory responses in ways that may affect tumor recurrence, underscoring the need for further research to optimize anesthetic protocols. The review offers clinical recommendations based on current evidence and identifies gaps in knowledge, proposing directions for future investigations. This comprehensive analysis aims to inform clinical practice and guide future research, ultimately improving long-term outcomes for colorectal cancer patients.

Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity.

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome's role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.

An Experimental Animal Study: Electroacupuncture Facilitates Antiviral Immunity Against Hepatitis B Virus Through the IFN-γ/JAK/STAT Axis.

Background: Chronic hepatitis B (CHB) remains a global health challenge, necessitating innovative therapeutic strategies. Enhancing the body's immune response against the hepatitis B virus (HBV) emerges as a fundamental strategy for achieving a functional cure. While acupuncture has shown potential in immune modulation, its specific anti-HBV effects are not well understood. This study evaluates the potential of electroacupuncture (EA) in HBV infection and explores its underlying immunological mechanisms using a mouse model. Methods: HBV-infected mice were established using the high-pressure hydrodynamic method and divided into four groups: normal saline (NS), EA, sham EA (SE), and tenofovir disoproxil fumarate (TF), with n = 6 per group. During treatment, blood was collected every Sunday via the orbital sinus to monitor HBV DNA, HBsAg, and HBeAg levels. Transcriptomics and metabolomics analyses were employed to unearth clues regarding EA's anti-HBV mechanism. Validation of these mechanisms included splenic T-cell flow analysis, Western blotting, RT-qPCR, immunofluorescence, and ELISA. Results: Serum HBV DNA levels decreased by 1.10, 0.19, and 1.98 log10 IU/mL in the EA, SE, and TF-treated mice, respectively, compared to the NS. Concurrently, the hepatic HBV DNA levels decreased by 1.09, 0.24, and 2.03 log10 IU/mL. EA also demonstrated superior inhibition of HBV antigens, with serum HBeAg levels decreasing by 43.86%, 8.74%, and 8.03%, and serum HBsAg levels decreasing by 28.01%, 0.26%, and 9.39% in the EA, SE, and TF groups, respectively. Further analysis through transcriptomics and metabolomics revealed that EA's anti-HBV effects primarily hinge on immune modulation, particularly the IFN-γ/JAK/STAT pathway and taurine metabolism. EA also increased the ratio of splenic CD8+ CD69+ and CD8+ IFN-γ+ T-cells while upregulating key proteins in the JAK/STAT pathway and cytokines associated with antiviral immunity. Conclusion: EA manifests inhibitory effects on HBV, particularly in antigen suppression, with its mode of action intricately linked to the regulation of IFN-γ/JAK/STAT.

Role of Neurotropic Viruses in Brain Metastasis of Breast Cancer: Mechanisms and Therapeutic Implications.

Neurotropic viruses have been implicated in altering the central nervous system microenvironment and promoting brain metastasis of breast cancer through complex interactions involving viral entry mechanisms, modulation of the blood-brain barrier, immune evasion, and alteration of the tumour microenvironment. This narrative review explores the molecular mechanisms by which neurotropic viruses such as Herpes Simplex Virus, Human Immunodeficiency Virus, Japanese Encephalitis Virus, and Rabies Virus facilitate brain metastasis, focusing on their ability to disrupt blood-brain barrier integrity, modulate immune responses, and create a permissive environment for metastatic cell survival and growth within the central nervous system. Current therapeutic implications and challenges in targeting neurotropic viruses to prevent or treat brain metastasis are discussed, highlighting the need for innovative strategies and multidisciplinary approaches in virology, oncology, and immunology.