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Genistein, a soy-derived isoflavone, has attracted considerable interest for its anti-inflammatory and anticancer properties. Chronic inflammation is a major driver of tumour initiation, progression, metastasis, and therapeutic resistance, creating a need for multi-target agents capable of modulating both inflammatory and oncogenic pathways. This review critically evaluates the molecular mechanisms, pharmacological basis, and translational prospects of genistein in inflammation-related cancers, incorporating recent advances in omics technologies and nanotechnology-based delivery systems. A comprehensive survey of the literature from major scientific databases was conducted, and evidence was assessed based on mechanistic depth, strength of data, and relevance to clinical translation. Genistein modulates multiple interconnected signalling pathways, including NF-κB, MAPK, PI3K/Akt, JAK/STAT, and apoptotic cascades, leading to reduced pro-inflammatory cytokine production, oxidative stress, and tumour cell proliferation. Epigenetic regulation, growth-factor pathway inhibition, and non-coding RNA modulation further contribute to its pleiotropic effects. Nanotechnology-based delivery platforms are being explored to improve their poor oral bioavailability and therapeutic performance in preclinical models. However, clinical translation remains limited by low bioavailability, context-dependent estrogenic activity, inter-individual metabolic variability, and the lack of large-scale, well-controlled clinical trials, standardized dosing, and validated biomarkers. Genistein represents a promising multi-target lead compound at the intersection of inflammation, immunology, and oncology, with future progress dependent on integrating multi-omics data and advanced delivery technologies for personalised clinical applications.
Genistein, a soy-derived isoflavone, has attracted considerable interest for its anti-inflammatory and anticancer properties. Chronic inflammation is a major driver of tumour initiation, progression, metastasis, and therapeutic resistance, creating a need for multi-target agents capable of modulating both inflammatory and oncogenic pathways. This review critically evaluates the molecular mechanisms, pharmacological basis, and translational prospects of genistein in inflammation-related cancers, incorporating recent advances in omics technologies and nanotechnology-based delivery systems. A comprehensive survey of the literature from major scientific databases was conducted, and evidence was assessed based on mechanistic depth, strength of data, and relevance to clinical translation. Genistein modulates multiple interconnected signalling pathways, including NF-κB, MAPK, PI3K/Akt, JAK/STAT, and apoptotic cascades, leading to reduced pro-inflammatory cytokine production, oxidative stress, and tumour cell proliferation. Epigenetic regulation, growth-factor pathway inhibition, and non-coding RNA modulation further contribute to its pleiotropic effects. Nanotechnology-based delivery platforms are being explored to improve their poor oral bioavailability and therapeutic performance in preclinical models. However, clinical translation remains limited by low bioavailability, context-dependent estrogenic activity, inter-individual metabolic variability, and the lack of large-scale, well-controlled clinical trials, standardized dosing, and validated biomarkers. Genistein represents a promising multi-target lead compound at the intersection of inflammation, immunology, and oncology, with future progress dependent on integrating multi-omics data and advanced delivery technologies for personalised clinical applications.
DOI: https://doi.org/10.37349/ei.2026.1003243
Immuno-materials, which represent a confluence of immunology and materials science, are dramatically transforming the fields of healthcare. Through the targeted modulation of immune responses, these innovative materials offer promising avenues for advancements in vaccine development, immunotherapy, tissue engineering, and diagnostics. This review examines the fundamental principles of immuno-materials, elucidating key concepts and methodologies pertinent to their development. We investigate strategies for engineering materials that can elicit customized immune responses, capable of both stimulation and suppression, and we discuss their potential roles as adjuvants, carriers, or scaffolds. Furthermore, we address the challenges and opportunities associated with the clinical translation of these materials, emphasizing the critical importance of biocompatibility, safety, and efficacy. This review aims to critically evaluate and contextualize the transformative potential of immuno-materials, mapping their journey from laboratory design to proven clinical applications in enhancing human health.
Immuno-materials, which represent a confluence of immunology and materials science, are dramatically transforming the fields of healthcare. Through the targeted modulation of immune responses, these innovative materials offer promising avenues for advancements in vaccine development, immunotherapy, tissue engineering, and diagnostics. This review examines the fundamental principles of immuno-materials, elucidating key concepts and methodologies pertinent to their development. We investigate strategies for engineering materials that can elicit customized immune responses, capable of both stimulation and suppression, and we discuss their potential roles as adjuvants, carriers, or scaffolds. Furthermore, we address the challenges and opportunities associated with the clinical translation of these materials, emphasizing the critical importance of biocompatibility, safety, and efficacy. This review aims to critically evaluate and contextualize the transformative potential of immuno-materials, mapping their journey from laboratory design to proven clinical applications in enhancing human health.
DOI: https://doi.org/10.37349/ei.2026.1003242
This article belongs to the special issue Immuno-Materials: at the interdisciplinary of immunology and materials
Autoimmune diseases (ADs) comprise a heterogeneous group of disorders characterised by a breakdown of immune tolerance and chronic immune-mediated tissue damage. Their onset and progression result from a complex interplay between genetic susceptibility, hormonal influences, immune regulatory mechanisms, and environmental exposures collectively referred to as the exposome. A striking feature of ADs is their pronounced sexual dimorphism, with a markedly higher prevalence in women for most conditions, alongside sex-specific differences in clinical presentation, severity, and prognosis. This review provides a comprehensive overview of the genetic and environmental determinants contributing to autoimmunity, with particular emphasis on how sex- and gender-related factors shape immune tolerance and disease susceptibility. We discuss central and peripheral tolerance mechanisms, the role of key regulators such as AIRE and FOXP3, sex chromosome-linked effects including X-chromosome inactivation, and the immunomodulatory impact of sex hormones across different life stages. Furthermore, we examine how environmental exposures, infections, and geographic variability interact with genetic background and sex-specific immune regulation to influence autoimmune disease risk. By integrating biological sex and gender-related factors within the framework of immune tolerance and the exposome, this review highlights the need for a sex-aware and personalised approach to understanding, diagnosing, and treating ADs.
Autoimmune diseases (ADs) comprise a heterogeneous group of disorders characterised by a breakdown of immune tolerance and chronic immune-mediated tissue damage. Their onset and progression result from a complex interplay between genetic susceptibility, hormonal influences, immune regulatory mechanisms, and environmental exposures collectively referred to as the exposome. A striking feature of ADs is their pronounced sexual dimorphism, with a markedly higher prevalence in women for most conditions, alongside sex-specific differences in clinical presentation, severity, and prognosis. This review provides a comprehensive overview of the genetic and environmental determinants contributing to autoimmunity, with particular emphasis on how sex- and gender-related factors shape immune tolerance and disease susceptibility. We discuss central and peripheral tolerance mechanisms, the role of key regulators such as AIRE and FOXP3, sex chromosome-linked effects including X-chromosome inactivation, and the immunomodulatory impact of sex hormones across different life stages. Furthermore, we examine how environmental exposures, infections, and geographic variability interact with genetic background and sex-specific immune regulation to influence autoimmune disease risk. By integrating biological sex and gender-related factors within the framework of immune tolerance and the exposome, this review highlights the need for a sex-aware and personalised approach to understanding, diagnosing, and treating ADs.
DOI: https://doi.org/10.37349/ei.2026.1003241
Pain is among the most prevalent and debilitating symptoms experienced by patients with cancer, significantly impairing functional status and overall quality of life. Its origin is multifactorial, involving direct tumor infiltration, treatment-induced tissue and neural injury, and immune-mediated inflammatory processes. This section examines the epidemiology of cancer-related pain, delineates its complex pathophysiology with particular focus on neuroimmune interactions, and reviews current pharmacological and interventional approaches for managing both acute and chronic pain in oncological settings. Advancing knowledge of immune-driven pain mechanisms holds promise for the development of more targeted, effective, and personalized analgesic strategies in cancer care.
Pain is among the most prevalent and debilitating symptoms experienced by patients with cancer, significantly impairing functional status and overall quality of life. Its origin is multifactorial, involving direct tumor infiltration, treatment-induced tissue and neural injury, and immune-mediated inflammatory processes. This section examines the epidemiology of cancer-related pain, delineates its complex pathophysiology with particular focus on neuroimmune interactions, and reviews current pharmacological and interventional approaches for managing both acute and chronic pain in oncological settings. Advancing knowledge of immune-driven pain mechanisms holds promise for the development of more targeted, effective, and personalized analgesic strategies in cancer care.
DOI: https://doi.org/10.37349/ei.2026.1003240
Atopic dermatitis is a chronic inflammatory skin condition characterized by immune dysregulation and dysfunction of the epidermal barrier. Although occludin, a vital tight junction protein, is essential for preserving barrier integrity, very little is known about its potential as a serum biomarker in atopic dermatitis. This pilot case-control study measured serum occludin levels in 30 adult atopic dermatitis patients and 30 age- and sex-matched healthy controls between May and August 2025, using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Findings showed serum occludin levels were significantly higher in atopic dermatitis patients (mean: 2.50 ± 1.10 ng/mL) compared to healthy controls (mean: 0.68 ± 0.69 ng/mL; p < 0.001), with levels showing a decreasing trend with age. Serum occludin exhibited high diagnostic performance [area under the curve (AUC) = 0.92] and represents a sensitive and specific, non-invasive biomarker for atopic dermatitis. These preliminary findings lay the groundwork for future studies exploring serum occludin as a potential biomarker for atopic dermatitis assessment.
Atopic dermatitis is a chronic inflammatory skin condition characterized by immune dysregulation and dysfunction of the epidermal barrier. Although occludin, a vital tight junction protein, is essential for preserving barrier integrity, very little is known about its potential as a serum biomarker in atopic dermatitis. This pilot case-control study measured serum occludin levels in 30 adult atopic dermatitis patients and 30 age- and sex-matched healthy controls between May and August 2025, using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Findings showed serum occludin levels were significantly higher in atopic dermatitis patients (mean: 2.50 ± 1.10 ng/mL) compared to healthy controls (mean: 0.68 ± 0.69 ng/mL; p < 0.001), with levels showing a decreasing trend with age. Serum occludin exhibited high diagnostic performance [area under the curve (AUC) = 0.92] and represents a sensitive and specific, non-invasive biomarker for atopic dermatitis. These preliminary findings lay the groundwork for future studies exploring serum occludin as a potential biomarker for atopic dermatitis assessment.
DOI: https://doi.org/10.37349/ei.2026.1003239
Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are microbial metabolites generated through the fermentation of dietary fibers by the gut microbiota and are increasingly recognized as critical regulators of host immune homeostasis. Beyond their metabolic roles, SCFAs exert potent immunomodulatory effects across mucosal tissues, including the periodontium, by shaping both innate and adaptive immune responses. This review synthesizes current evidence on the dual roles of SCFAs in periodontal health and disease, with particular emphasis on the contrasting effects of systemically derived versus locally accumulated SCFAs within periodontal tissues. Gut-derived SCFAs absorbed into the circulation modulate immune function through activation of G protein-coupled receptors (GPR41, GPR43, and GPR109A) and inhibition of histone deacetylases. These pathways promote regulatory T cell differentiation, skew macrophage polarization toward anti-inflammatory M2 phenotypes, and regulate neutrophil and dendritic cell activity. These effects support immune tolerance, epithelial barrier integrity, and resolution of inflammation, thereby contributing to periodontal homeostasis. In contrast, SCFAs produced locally within periodontal pockets can reach millimolar concentrations that disrupt epithelial and fibroblast function, induce oxidative stress, and amplify inflammatory signalling, ultimately driving tissue destruction and disease progression. Emerging evidence links gut microbial composition and systemic SCFA availability to periodontal inflammation through immune and neuroimmune crosstalk, supporting a biologically plausible gut-oral axis. Translational strategies aimed at harnessing the immunoregulatory properties of SCFAs are critically evaluated in this review. While these approaches are promising, challenges related to dosing, delivery, inter-individual variability, and limited human interventional data remain, underscoring the need for rigorously designed translational studies.
Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are microbial metabolites generated through the fermentation of dietary fibers by the gut microbiota and are increasingly recognized as critical regulators of host immune homeostasis. Beyond their metabolic roles, SCFAs exert potent immunomodulatory effects across mucosal tissues, including the periodontium, by shaping both innate and adaptive immune responses. This review synthesizes current evidence on the dual roles of SCFAs in periodontal health and disease, with particular emphasis on the contrasting effects of systemically derived versus locally accumulated SCFAs within periodontal tissues. Gut-derived SCFAs absorbed into the circulation modulate immune function through activation of G protein-coupled receptors (GPR41, GPR43, and GPR109A) and inhibition of histone deacetylases. These pathways promote regulatory T cell differentiation, skew macrophage polarization toward anti-inflammatory M2 phenotypes, and regulate neutrophil and dendritic cell activity. These effects support immune tolerance, epithelial barrier integrity, and resolution of inflammation, thereby contributing to periodontal homeostasis. In contrast, SCFAs produced locally within periodontal pockets can reach millimolar concentrations that disrupt epithelial and fibroblast function, induce oxidative stress, and amplify inflammatory signalling, ultimately driving tissue destruction and disease progression. Emerging evidence links gut microbial composition and systemic SCFA availability to periodontal inflammation through immune and neuroimmune crosstalk, supporting a biologically plausible gut-oral axis. Translational strategies aimed at harnessing the immunoregulatory properties of SCFAs are critically evaluated in this review. While these approaches are promising, challenges related to dosing, delivery, inter-individual variability, and limited human interventional data remain, underscoring the need for rigorously designed translational studies.
DOI: https://doi.org/10.37349/ei.2026.1003238
For decades, vaccines have been a key tool against microbial infections. However, the high cost of production and purification renders vaccines largely inaccessible to many developing countries. The limitations of conventional vaccines can be overcome by edible vaccines. To produce an oral vaccine, favourable vectors, such as plants and probiotics, are used. Recent studies have revealed the immunomodulatory effects of probiotics. To improve the efficacy of these vaccines, several adjuvant approaches have been employed. Postbiotics can be used as promising therapy for preventing infections and enhancing the host immune system due to their unique biochemical and microbial-derived properties. In this review, we discuss the feasibility of postbiotics as adjuvants for oral vaccines, highlighting their mechanisms of action, safety profile, and potential to enhance both mucosal and systemic immune responses.
For decades, vaccines have been a key tool against microbial infections. However, the high cost of production and purification renders vaccines largely inaccessible to many developing countries. The limitations of conventional vaccines can be overcome by edible vaccines. To produce an oral vaccine, favourable vectors, such as plants and probiotics, are used. Recent studies have revealed the immunomodulatory effects of probiotics. To improve the efficacy of these vaccines, several adjuvant approaches have been employed. Postbiotics can be used as promising therapy for preventing infections and enhancing the host immune system due to their unique biochemical and microbial-derived properties. In this review, we discuss the feasibility of postbiotics as adjuvants for oral vaccines, highlighting their mechanisms of action, safety profile, and potential to enhance both mucosal and systemic immune responses.
DOI: https://doi.org/10.37349/ei.2026.1003237
Pneumococcal disease remains a major global health challenge despite the availability of polysaccharide and conjugate vaccines. Although these platforms have reduced invasive disease, their limitations, such as poor immunogenicity in infants, lack of durable protection, and restricted coverage, highlight the need to explore innovative preventive strategies. Next-generation vaccines that provide comprehensive protection, sustained immunity, and cost-effectiveness are urgently required. Live attenuated vaccines (LAVs) represent a promising frontier in this effort, with recent advances focused on overcoming developmental and safety challenges. This review highlights the evolving pneumococcal vaccine landscape, with emphasis on LAV strategies. We summarize the strengths and shortcomings of current vaccines, examine recent advances in LAV development, including key aspects of attenuation, immune-protective mechanisms, and delivery approaches. LAVs demonstrate potential to induce balanced mucosal, humoral, and cellular immunity, addressing critical gaps left by existing platforms. Key challenges related to genetic stability, safety, and translational applicability are also discussed. By synthesizing established knowledge and highlighting advancements, this review underscores the promise of LAVs as next-generation candidates that can provide broader, longer-lasting protection against pneumococcal disease.
Pneumococcal disease remains a major global health challenge despite the availability of polysaccharide and conjugate vaccines. Although these platforms have reduced invasive disease, their limitations, such as poor immunogenicity in infants, lack of durable protection, and restricted coverage, highlight the need to explore innovative preventive strategies. Next-generation vaccines that provide comprehensive protection, sustained immunity, and cost-effectiveness are urgently required. Live attenuated vaccines (LAVs) represent a promising frontier in this effort, with recent advances focused on overcoming developmental and safety challenges. This review highlights the evolving pneumococcal vaccine landscape, with emphasis on LAV strategies. We summarize the strengths and shortcomings of current vaccines, examine recent advances in LAV development, including key aspects of attenuation, immune-protective mechanisms, and delivery approaches. LAVs demonstrate potential to induce balanced mucosal, humoral, and cellular immunity, addressing critical gaps left by existing platforms. Key challenges related to genetic stability, safety, and translational applicability are also discussed. By synthesizing established knowledge and highlighting advancements, this review underscores the promise of LAVs as next-generation candidates that can provide broader, longer-lasting protection against pneumococcal disease.
DOI: https://doi.org/10.37349/ei.2026.1003236
This article belongs to the special issue Novel Vaccines development for Emerging, Acute, and Re-emerging Infectious Diseases
Pulsed radiofrequency (PRF) has emerged as a promising and versatile technology in pain management and immunological modulation. PRFʼs effects extend beyond pain modulation, demonstrating the ability to regulate inflammatory processes through cytokine modulation, reduction of microglial hyperactivity, and promotion of autophagy. These mechanisms position PRF as a potential therapeutic tool not only for neuropathic and musculoskeletal pain but also for conditions associated with neuroinflammation and immune dysfunction, including chronic inflammatory and degenerative diseases. Clinically, PRF has demonstrated potential in alleviating neuropathic pain in several clinical studies—including a limited number of small RCTs. However, most of the available evidence remains of low methodological quality, with many studies being observational, retrospective, or underpowered. Moreover, the lack of standardized protocols remains a barrier to its broader adoption. Establishing evidence-based guidelines and enhancing practitioner expertise are critical to ensuring consistent and optimal patient outcomes. Future research should focus on optimizing PRF technical parameters, elucidating molecular mechanisms, and expanding its clinical applications. Integrating PRF with emerging therapies, such as orthobiologics, biological drugs, and electrical stimulation, may further enhance its efficacy. Moreover, advancements in predictive biomarkers and device technologies hold promise for personalized treatments, improving the precision and effectiveness of PRF interventions. This narrative review explores the primary clinical applications, underlying biological mechanisms, and potential future directions of PRF, emphasizing its ability to address complex therapeutic challenges.
Pulsed radiofrequency (PRF) has emerged as a promising and versatile technology in pain management and immunological modulation. PRFʼs effects extend beyond pain modulation, demonstrating the ability to regulate inflammatory processes through cytokine modulation, reduction of microglial hyperactivity, and promotion of autophagy. These mechanisms position PRF as a potential therapeutic tool not only for neuropathic and musculoskeletal pain but also for conditions associated with neuroinflammation and immune dysfunction, including chronic inflammatory and degenerative diseases. Clinically, PRF has demonstrated potential in alleviating neuropathic pain in several clinical studies—including a limited number of small RCTs. However, most of the available evidence remains of low methodological quality, with many studies being observational, retrospective, or underpowered. Moreover, the lack of standardized protocols remains a barrier to its broader adoption. Establishing evidence-based guidelines and enhancing practitioner expertise are critical to ensuring consistent and optimal patient outcomes. Future research should focus on optimizing PRF technical parameters, elucidating molecular mechanisms, and expanding its clinical applications. Integrating PRF with emerging therapies, such as orthobiologics, biological drugs, and electrical stimulation, may further enhance its efficacy. Moreover, advancements in predictive biomarkers and device technologies hold promise for personalized treatments, improving the precision and effectiveness of PRF interventions. This narrative review explores the primary clinical applications, underlying biological mechanisms, and potential future directions of PRF, emphasizing its ability to address complex therapeutic challenges.
DOI: https://doi.org/10.37349/ei.2026.1003235
Vaccines can be highly safe and effective tools for disease prevention. However, improvements in the areas of cost, ease of manufacture, distribution, and administration are sought in the next generation of vaccine platforms. A promising candidate is the recombinant flagellin fusion protein platform, which comprises a protein antigen of interest genetically fused to the bacterial protein flagellin. As flagellin stimulates two distinct pattern recognition receptors of the human innate immune system (Toll-like receptor 5 and nucleotide-binding and oligomerization domain-like receptor family apoptosis inhibitory protein) and contains helper T-cell epitopes, it is capable of serving as both a carrier and an adjuvant for the target antigen. Studies in animal models and human clinical trials have shown that flagellin fusion proteins can induce diverse humoral (including various subtypes of IgG), mucosal (including secreted IgA), and cell-mediated (TH1 and TH2 CD4+ helper T-cell and CD8+ cytotoxic T-cell) responses to the covalently linked antigen. Such fusions are also capable of eliciting protective immunity in diverse experimental models of infection and cancer. They are effective via numerous routes of administration, including intranasal delivery, without the requirement for adjuvant or complex delivery vehicles. This review aims to cover recent progress in the investigation of flagellin fusion proteins for their potential to stimulate humoral and cellular immune responses to partner antigens, and their prospects for the prevention or treatment of viral infections and cancer.
Vaccines can be highly safe and effective tools for disease prevention. However, improvements in the areas of cost, ease of manufacture, distribution, and administration are sought in the next generation of vaccine platforms. A promising candidate is the recombinant flagellin fusion protein platform, which comprises a protein antigen of interest genetically fused to the bacterial protein flagellin. As flagellin stimulates two distinct pattern recognition receptors of the human innate immune system (Toll-like receptor 5 and nucleotide-binding and oligomerization domain-like receptor family apoptosis inhibitory protein) and contains helper T-cell epitopes, it is capable of serving as both a carrier and an adjuvant for the target antigen. Studies in animal models and human clinical trials have shown that flagellin fusion proteins can induce diverse humoral (including various subtypes of IgG), mucosal (including secreted IgA), and cell-mediated (TH1 and TH2 CD4+ helper T-cell and CD8+ cytotoxic T-cell) responses to the covalently linked antigen. Such fusions are also capable of eliciting protective immunity in diverse experimental models of infection and cancer. They are effective via numerous routes of administration, including intranasal delivery, without the requirement for adjuvant or complex delivery vehicles. This review aims to cover recent progress in the investigation of flagellin fusion proteins for their potential to stimulate humoral and cellular immune responses to partner antigens, and their prospects for the prevention or treatment of viral infections and cancer.
DOI: https://doi.org/10.37349/ei.2026.1003234
This article belongs to the special issue Novel Vaccines development for Emerging, Acute, and Re-emerging Infectious Diseases
Aim:
The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Methods:
Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS).
Results:
S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison, L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity.
Conclusions:
Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects of S. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation.
Aim:
The benefit of topical application of probiotics on pain and itching associated with skin disorders has become an increasingly intriguing topic in recent years. These effects are mainly associated with the anti-inflammatory activity of probiotics. Given the crucial role of the endocannabinoid system (ECS) in skin pathophysiology, here, the ability of Streptococcus thermophilus was evaluated, in comparison with Lactobacillus acidophilus, to inhibit two enzymes involved in endocannabinoid (eCB) degradation: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).
Methods:
Bacterial lysates were obtained from both probiotics. FAAH and MAGL activities were assayed using fluorometric and colorimetric methods. The effect of probiotic lysates on FAAH and MAGL activities was also evaluated on human keratinocytes stimulated with lipopolysaccharide (LPS).
Results:
S. thermophilus inhibited both FAAH and MAGL, although to varying extents. In comparison, L. acidophilus had a minimal effect on FAAH and did not influence MAGL activity.
Conclusions:
Although preliminary, our findings suggest that S. thermophilus may exert both potential analgesic and anti-inflammatory effects by modulating the ECS and reducing the degradation of EC, known to play a key role in immune regulation and inflammation. Results presented confirm the selective actions of probiotics and propose a novel mechanism that may contribute to the beneficial effects of S. thermophilus in alleviating signs and symptoms associated with inflammatory skin conditions. Our evidence shows significant inhibitory activity of S. thermophilus on FAAH and MAGL activity, suggesting its ability to influence skin conditions by modulating ECS and preventing the eCB degradation.
DOI: https://doi.org/10.37349/ei.2025.1003233
This article belongs to the special issue Immunology and Pain
Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research.
Inflammatory bowel disease (IBD), consisting of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract with significant clinical impact, leading to debilitating symptoms, impaired quality of life, and an increased risk of complications such as colorectal cancer. This review provides a comprehensive overview of current and emerging therapeutic strategies for IBD. We conducted a narrative review to explore therapeutic advances in IBD treatment, focusing on mechanisms of action, clinical development, and current therapeutic challenges. We analyzed existing knowledge on clinical drug development for IBD, up to July 2025. Our search encompassed databases including PubMed, ClinicalTrials.gov, and Google Scholar, using keywords such as “Inflammatory bowel disease”, “Crohn’s disease”, “Ulcerative colitis”, “therapeutics”, and relevant drug names. We delve into key progress in approved drugs in recent years, including biologic and targeted small molecule therapies, which have advanced the treatment paradigms by offering more precise targeting of inflammatory pathways. This review also covers investigational drugs in clinical development, including biologics and small molecules against novel molecular targets, cell and gene therapies, precision medicine approaches, and microbiome-based interventions. Those novel therapies could potentially address unmet medical needs by achieving deeper and more durable responses, inducing remission, preventing disease progression, and ultimately improving long-term patient outcomes. This review summarizes the latest progress in IBD treatment, outlines the advantages, pitfalls, and research prospects of various drugs and therapies, aiming to provide a foundational understanding for both clinical decision-making and future IBD research.
DOI: https://doi.org/10.37349/ei.2025.1003232
This article belongs to the special issue Advances in Cellular and Molecular Treatment of Autoimmune Diseases
Aim:
To determine whether PepTivator® melanoma-associated antigen-A3 (MAGE-A3) primes early T-cell activation and memory skewing in human peripheral blood mononuclear cells (PBMCs).
Methods:
PBMCs from 10 donors were stimulated with MAGE-A3 (manufacturer-recommended dose), negative control (NC), or CD3/CD28 and CytoStim™ (PC: positive control). Activation [CD69, CD25, HLA-DR (human leukocyte antigen-DR isotype)], proliferation, cytokines [24 h; GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN-γ (interferon-gamma), IL-2 (interleukin-2), TNF-α (tumor necrosis factor-alpha)], and memory phenotypes (CD45RO/CD27 at days 0/7/14) were quantified by flow cytometry and MACSPlex. Paired statistics used repeated-measures models with Šidák correction; cytokines were analyzed on log10 scale.
Results:
MAGE-A3 significantly increased early activation (CD69 ↑, CD25 ↑) and modestly increased proliferation, with selective IL-2/TNF-α rise and minimal IFN-γ and modest HLA-DR. Across two weeks, 6/10 donors showed increased central memory T cell (TCM)/effector memory T cell (TEM) with a corresponding decline in naïve cells relative to NC. Variability across donors was evident.
Conclusions:
MAGE-A3 primes partial activation and memory skewing of human T cells in vitro, suggesting utility as a component antigen that likely benefits from professional antigen-presenting cell (APC) presentation and/or costimulation. We discuss limitations (single dose, in vitro context, donor variability) and implications for future dose-response, HLA-stratified, and APC-supported studies.
Aim:
To determine whether PepTivator® melanoma-associated antigen-A3 (MAGE-A3) primes early T-cell activation and memory skewing in human peripheral blood mononuclear cells (PBMCs).
Methods:
PBMCs from 10 donors were stimulated with MAGE-A3 (manufacturer-recommended dose), negative control (NC), or CD3/CD28 and CytoStim™ (PC: positive control). Activation [CD69, CD25, HLA-DR (human leukocyte antigen-DR isotype)], proliferation, cytokines [24 h; GM-CSF (granulocyte-macrophage colony-stimulating factor), IFN-γ (interferon-gamma), IL-2 (interleukin-2), TNF-α (tumor necrosis factor-alpha)], and memory phenotypes (CD45RO/CD27 at days 0/7/14) were quantified by flow cytometry and MACSPlex. Paired statistics used repeated-measures models with Šidák correction; cytokines were analyzed on log10 scale.
Results:
MAGE-A3 significantly increased early activation (CD69 ↑, CD25 ↑) and modestly increased proliferation, with selective IL-2/TNF-α rise and minimal IFN-γ and modest HLA-DR. Across two weeks, 6/10 donors showed increased central memory T cell (TCM)/effector memory T cell (TEM) with a corresponding decline in naïve cells relative to NC. Variability across donors was evident.
Conclusions:
MAGE-A3 primes partial activation and memory skewing of human T cells in vitro, suggesting utility as a component antigen that likely benefits from professional antigen-presenting cell (APC) presentation and/or costimulation. We discuss limitations (single dose, in vitro context, donor variability) and implications for future dose-response, HLA-stratified, and APC-supported studies.
DOI: https://doi.org/10.37349/ei.2025.1003231
Aim:
Develop A/H1N1pdm09-based live attenuated influenza vaccines (LAIVs) presenting chimeric hemagglutinin (HA) fused to fragments of Streptococcus pneumoniae (PspA, Spr1875) or S. agalactiae (ScaAB) to elicit combined anti-influenza and anti-bacterial immunity.
Methods:
Recombinant LAIVs were generated by reverse genetics. Replicative fitness was measured in embryonated chicken eggs (CE; log10 EID50/0.1 mL, n = 5 per delution) and MDCK cells (log10 TCID50/mL, n = 5). BALB/c mice (n = 20 per group; serology n = 6 per group; lung titers n = 5 per group) received intranasal 106 EID50. Systemic IgG and mucosal IgA to influenza and to the recombinant pneumococcal peptide were quantified by ELISA (GMT ± SD). Early cytokine responses were profiled in THP-1 cells.
Results:
All recombinant strains replicated in CE at 33°C but were temperature-sensitive at 39°C. H1-ScaAB retained relatively high replication and exhibited a cold-adapted phenotype despite a large N-terminal insert. In MDCK cells, H1-PspA showed significantly reduced replication compared with the parental LAIV. In mouse lungs, replication on day 3 post-immunization was significantly lower for H1-ScaAB and H1-PspA compared with the parental LAIV strain (p < 0.05). The parental LAIV induced robust systemic anti-influenza IgG and, uniquely for H1-ScaAB, significant mucosal anti-influenza IgA (p < 0.05). H1-Spr generated stronger antibody responses to the inserted pneumococcal peptide (p < 0.05). THP-1 assays revealed construct-specific cytokine patterns (unmodified H1N1: highest IFN-α; H1-Spr: elevated IL-6; H1-ScaAB: greatest MCP-1).
Conclusions:
Multiple A/H1N1pdm09-based recombinant LAIVs with chimeric HA can replicate in eggs and murine respiratory tract and induce dual influenza/pneumococcal antigen responses. Expanded biophysical validation, functional antibody assays and challenge studies are needed to optimize insert design without compromising viral fitness.
Aim:
Develop A/H1N1pdm09-based live attenuated influenza vaccines (LAIVs) presenting chimeric hemagglutinin (HA) fused to fragments of Streptococcus pneumoniae (PspA, Spr1875) or S. agalactiae (ScaAB) to elicit combined anti-influenza and anti-bacterial immunity.
Methods:
Recombinant LAIVs were generated by reverse genetics. Replicative fitness was measured in embryonated chicken eggs (CE; log10 EID50/0.1 mL, n = 5 per delution) and MDCK cells (log10 TCID50/mL, n = 5). BALB/c mice (n = 20 per group; serology n = 6 per group; lung titers n = 5 per group) received intranasal 106 EID50. Systemic IgG and mucosal IgA to influenza and to the recombinant pneumococcal peptide were quantified by ELISA (GMT ± SD). Early cytokine responses were profiled in THP-1 cells.
Results:
All recombinant strains replicated in CE at 33°C but were temperature-sensitive at 39°C. H1-ScaAB retained relatively high replication and exhibited a cold-adapted phenotype despite a large N-terminal insert. In MDCK cells, H1-PspA showed significantly reduced replication compared with the parental LAIV. In mouse lungs, replication on day 3 post-immunization was significantly lower for H1-ScaAB and H1-PspA compared with the parental LAIV strain (p < 0.05). The parental LAIV induced robust systemic anti-influenza IgG and, uniquely for H1-ScaAB, significant mucosal anti-influenza IgA (p < 0.05). H1-Spr generated stronger antibody responses to the inserted pneumococcal peptide (p < 0.05). THP-1 assays revealed construct-specific cytokine patterns (unmodified H1N1: highest IFN-α; H1-Spr: elevated IL-6; H1-ScaAB: greatest MCP-1).
Conclusions:
Multiple A/H1N1pdm09-based recombinant LAIVs with chimeric HA can replicate in eggs and murine respiratory tract and induce dual influenza/pneumococcal antigen responses. Expanded biophysical validation, functional antibody assays and challenge studies are needed to optimize insert design without compromising viral fitness.
DOI: https://doi.org/10.37349/ei.2025.1003230
This article belongs to the special issue Old and New Paradigms in Viral Vaccinology
Killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules play an essential role in regulating immune responses against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. HLA-KIRs interactions are crucial for activating and inhibiting the natural killer (NK) cell system through a modulation that shapes these cells to kill infected cells and release cytokines. Regulation underlies the anti-viral function of the NK cell and profoundly affects viral clearance, immune evasion, and the course of disease. Activating KIRs such as KIR2DS1 and KIR3DS1 cooperate with specific HLA ligands in boosting NK cell responses against the virus, thereby facilitating viral elimination. In contrast, inhibitory KIRs like KIR2DL1 and KIR3DL1 bind to HLA-C2 and HLA-Bw4, respectively, imposing a dampening influence on NK cell activation, which allows the virus to persist and progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). These variations in KIRs and HLA genes will also affect an individual’s susceptibility to infections, disease severity, and their response to antiviral therapies. Observation of the role of KIRs and their interaction with HLA at the immunogenetic level provides valuable insight into host-virus dynamics and opens up many therapeutic avenues. Targeting immunotherapies toward NK cell pathways and developing personalized medicine may boost antiviral immune responses and improve treatment outcomes in chronic viral hepatitis patients. This review recognizes HLA-KIRs interactions as potent biomarkers for disease progression and determining treatment strategies.
Killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules play an essential role in regulating immune responses against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. HLA-KIRs interactions are crucial for activating and inhibiting the natural killer (NK) cell system through a modulation that shapes these cells to kill infected cells and release cytokines. Regulation underlies the anti-viral function of the NK cell and profoundly affects viral clearance, immune evasion, and the course of disease. Activating KIRs such as KIR2DS1 and KIR3DS1 cooperate with specific HLA ligands in boosting NK cell responses against the virus, thereby facilitating viral elimination. In contrast, inhibitory KIRs like KIR2DL1 and KIR3DL1 bind to HLA-C2 and HLA-Bw4, respectively, imposing a dampening influence on NK cell activation, which allows the virus to persist and progress to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). These variations in KIRs and HLA genes will also affect an individual’s susceptibility to infections, disease severity, and their response to antiviral therapies. Observation of the role of KIRs and their interaction with HLA at the immunogenetic level provides valuable insight into host-virus dynamics and opens up many therapeutic avenues. Targeting immunotherapies toward NK cell pathways and developing personalized medicine may boost antiviral immune responses and improve treatment outcomes in chronic viral hepatitis patients. This review recognizes HLA-KIRs interactions as potent biomarkers for disease progression and determining treatment strategies.
DOI: https://doi.org/10.37349/ei.2025.1003229
This article belongs to the special issue Immunogenetics of Chronic Illnesses
Tumor-infiltrating lymphocytes (TILs) play a critical role in the ability of the immune system to combat cancer, offering a foundation for personalized immunotherapies. However, the effectiveness of TILs is often reduced by problems like becoming less active, the tumor making the immune system weaker, and not lasting long in the tumor environment. Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor sequencing (scTCR-seq), and mass cytometry (CyTOF), have revolutionized our understanding of TIL heterogeneity and dynamics. These tools offer new perspectives on the diverse phenotypes, functional states, and spatial organization of TILs, enabling the identification of key exhaustion markers, regulatory pathways, and neoantigen-specific clones. Concurrently, genetic reprogramming strategies have emerged to address TIL limitations by reversing exhaustion, enhancing metabolic resilience, and improving persistence in vivo. This review explores the synergistic integration of single-cell technologies and genetic engineering in refining TIL-based therapies. We talk about how spatial transcriptomics can help us understand how TILs work in different areas of the body and how changing their epigenetics can help them become more effective at fighting cancer. Additionally, we highlight emerging approaches to overcome immunosuppressive barriers in the tumor microenvironment (TME), including targeting regulatory immune cells, neutralizing suppressive cytokines, and enhancing antigen presentation. Together, these strategies promise to unlock the full therapeutic potential of TILs, paving the way for more effective and durable cancer immunotherapy.
Tumor-infiltrating lymphocytes (TILs) play a critical role in the ability of the immune system to combat cancer, offering a foundation for personalized immunotherapies. However, the effectiveness of TILs is often reduced by problems like becoming less active, the tumor making the immune system weaker, and not lasting long in the tumor environment. Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor sequencing (scTCR-seq), and mass cytometry (CyTOF), have revolutionized our understanding of TIL heterogeneity and dynamics. These tools offer new perspectives on the diverse phenotypes, functional states, and spatial organization of TILs, enabling the identification of key exhaustion markers, regulatory pathways, and neoantigen-specific clones. Concurrently, genetic reprogramming strategies have emerged to address TIL limitations by reversing exhaustion, enhancing metabolic resilience, and improving persistence in vivo. This review explores the synergistic integration of single-cell technologies and genetic engineering in refining TIL-based therapies. We talk about how spatial transcriptomics can help us understand how TILs work in different areas of the body and how changing their epigenetics can help them become more effective at fighting cancer. Additionally, we highlight emerging approaches to overcome immunosuppressive barriers in the tumor microenvironment (TME), including targeting regulatory immune cells, neutralizing suppressive cytokines, and enhancing antigen presentation. Together, these strategies promise to unlock the full therapeutic potential of TILs, paving the way for more effective and durable cancer immunotherapy.
DOI: https://doi.org/10.37349/ei.2025.1003227
Innate lymphoid cells are lymphocytes that are neither T cells nor B cells. They are relatively rare in lymphoid tissues and peripheral blood and are distinguished by their absence of an adaptive antigen receptor. In the present study, we describe the mechanisms underlying the generation of the various cell populations and highlight the functional importance of their plasticity. These cells are indeed capable of transdifferentiating from one type to another. This adds complexity to their functional program, and this feature appears to be crucial for adapting and modulating immune responses under different conditions. These lymphoid cells are of great hematological interest due to their pathophysiological and therapeutic role in many onco-hematological pathologies such as acute myeloid leukemia, multiple myeloma, and several types of lymphomas. In hematological disorders, innate lymphoid cells may exert differential effects on the pathogenesis of hematologic malignancies. Furthermore, within the same disease, certain cell populations have been shown to play a protective role in antitumor immune responses, whereas others appear to suppress these responses. This review aims to provide an integrated description of innate lymphoid cells, their alterations in hematological malignancies, and potential preventive strategies, by proposing new specific targets for correcting anomalies. We also discuss the use of innate lymphoid cells as new therapies by applying chimeric antigen receptor-modified natural killer cells. We examine the current knowledge and outline future perspectives.
Innate lymphoid cells are lymphocytes that are neither T cells nor B cells. They are relatively rare in lymphoid tissues and peripheral blood and are distinguished by their absence of an adaptive antigen receptor. In the present study, we describe the mechanisms underlying the generation of the various cell populations and highlight the functional importance of their plasticity. These cells are indeed capable of transdifferentiating from one type to another. This adds complexity to their functional program, and this feature appears to be crucial for adapting and modulating immune responses under different conditions. These lymphoid cells are of great hematological interest due to their pathophysiological and therapeutic role in many onco-hematological pathologies such as acute myeloid leukemia, multiple myeloma, and several types of lymphomas. In hematological disorders, innate lymphoid cells may exert differential effects on the pathogenesis of hematologic malignancies. Furthermore, within the same disease, certain cell populations have been shown to play a protective role in antitumor immune responses, whereas others appear to suppress these responses. This review aims to provide an integrated description of innate lymphoid cells, their alterations in hematological malignancies, and potential preventive strategies, by proposing new specific targets for correcting anomalies. We also discuss the use of innate lymphoid cells as new therapies by applying chimeric antigen receptor-modified natural killer cells. We examine the current knowledge and outline future perspectives.
DOI: https://doi.org/10.37349/ei.2025.1003226
Background:
Oral squamous cell carcinoma (OSCC), a significant health burden in developing nations, is linked to risk factors such as tobacco use, alcohol consumption, betel nut chewing, HPV infection, and genetic susceptibility. A hallmark of OSCC is impaired T cell function, driven in part by the PD-L1/PD-1 immune checkpoint pathway, which enables tumor immune evasion and progression. Despite growing interest in immunotherapy, a focused synthesis of PD-L1 expression and its clinical implications in OSCC remains limited. This review aims to consolidate existing evidence on PD-L1 in OSCC, evaluating its expression patterns, correlation with disease progression, and therapeutic relevance.
Methods:
A systematic search was conducted across multiple databases to identify studies examining PD-L1 expression in OSCC and its relationship with clinicopathological parameters and immune response.
Results:
The findings revealed a higher PD-L1 positivity in female patients, non-smokers, and non-drinkers. Positive PD-L1 expression rate correlated with poor differentiation, lymph node metastasis, and advanced TNM stage. Although it didn’t significantly impact overall survival, higher PD-L1 expression was observed in HPV-positive patients and correlated with increased CD8+ TIL levels.
Discussion:
Understanding the role of PD-L1 in OSCC elucidates immune evasion mechanisms and offers insights into potential treatments, such as checkpoint inhibitors, for personalized therapies and innovative cancer treatments. This comprehensive synthesis provides valuable insights into the complex interplay between PD-L1 expression and OSCC progression, laying the groundwork for additional studies in this area.
Background:
Oral squamous cell carcinoma (OSCC), a significant health burden in developing nations, is linked to risk factors such as tobacco use, alcohol consumption, betel nut chewing, HPV infection, and genetic susceptibility. A hallmark of OSCC is impaired T cell function, driven in part by the PD-L1/PD-1 immune checkpoint pathway, which enables tumor immune evasion and progression. Despite growing interest in immunotherapy, a focused synthesis of PD-L1 expression and its clinical implications in OSCC remains limited. This review aims to consolidate existing evidence on PD-L1 in OSCC, evaluating its expression patterns, correlation with disease progression, and therapeutic relevance.
Methods:
A systematic search was conducted across multiple databases to identify studies examining PD-L1 expression in OSCC and its relationship with clinicopathological parameters and immune response.
Results:
The findings revealed a higher PD-L1 positivity in female patients, non-smokers, and non-drinkers. Positive PD-L1 expression rate correlated with poor differentiation, lymph node metastasis, and advanced TNM stage. Although it didn’t significantly impact overall survival, higher PD-L1 expression was observed in HPV-positive patients and correlated with increased CD8+ TIL levels.
Discussion:
Understanding the role of PD-L1 in OSCC elucidates immune evasion mechanisms and offers insights into potential treatments, such as checkpoint inhibitors, for personalized therapies and innovative cancer treatments. This comprehensive synthesis provides valuable insights into the complex interplay between PD-L1 expression and OSCC progression, laying the groundwork for additional studies in this area.
DOI: https://doi.org/10.37349/ei.2025.1003228
This article belongs to the special issue The Role of Immune Checkpoint Molecules in Cancer and Hematological Malignancies
DOI: https://doi.org/10.37349/ei.2025.1003225
Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered.
Cancer treatment regimens are significantly more intricate than commonly perceived. Nonetheless, both immunotherapy and chemotherapy may produce adverse consequences. Immunotherapy represents a significant advancement in the battle against cancer; nonetheless, it is not devoid of challenges. This research elucidates the mechanisms underlying immunotherapy-induced cardiovascular damage, highlighting the significant role of immune regulators, such as soluble urokinase plasminogen activator receptor (suPAR), in inducing vascular leakage. We also examine the role of matrix metalloproteinase (MMP14/15) in this process, and antigens associated with cardiovascular illness and malignancies, including native proteins, mutated tumor antigens, and viral components. Besides, we studied predictive biomarkers, such as circulating T-cell populations associated with the probability of myocarditis. We discuss treatment approaches and strategies to mitigate these issues, particularly through the use of antihypertensive medications to reduce their impact. Losartan alters the tumor microenvironment (TME) to improve immunotherapy. It restores immune effector cells in triple-negative breast cancer (TNBC), overcomes resistance in unresponsive tumors, and modifies TMEs’ immune system suppression in ovarian cancer and melanoma. It is important to note that its effects differ by cancer kind. It may promote fibrosarcoma tumor growth and improve cholangiocarcinoma treatment. This shows that losartan’s dangers in cancer treatment should be carefully considered and that more research is needed. This suggests that there must be careful consideration of the potential risks associated with losartan use in cancer treatment and underscores the requirement for additional research on this topic. This study may enhance our comprehension and management of cardiovascular adverse effects in cancer immunotherapy by integrating novel insights on immunological predictors and vascular dysfunction. Experts assert that oncology programs must provide and promote continuous monitoring of cardiac health for breast cancer patients. To mitigate the risk of cardiovascular disease in this demographic, comprehensive patient care must be administered.
DOI: https://doi.org/10.37349/ei.2025.1003224
This article belongs to the special issue The Role of Immune Checkpoint Molecules in Cancer and Hematological Malignancies
