Selective IgG4 deficiency and autoimmune cytopenias

Fibromyalgia syndrome and the immune system: a review with comparative perspectives on chronic immune-related syndromes including CFS/ME and IBS

Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, cognitive impairments, and sleep disturbances. Although traditionally considered psychogenic, recent research supports a multifactorial etiology involving central nervous system (CNS) dysregulation and significant immune involvement. This narrative review synthesizes current evidence regarding the role of immune mechanisms in FMS, with comparative insights into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and irritable bowel syndrome (IBS)—previously grouped under functional somatic syndromes (FSS). In FMS, immune dysregulation is evidenced by elevated levels of pro-inflammatory cytokines (e.g., IL-6, IL-8, TNF-α) and decreased anti-inflammatory mediators such as IL-10, contributing to symptomatology including pain amplification and fatigue. Neuroinflammation, as indicated by microglial activation in pain-processing CNS regions, further supports the role of immune signaling in central sensitization. Other contributing factors include oxidative stress, mitochondrial dysfunction, and immune cell alterations, particularly involving regulatory T cells and natural killer (NK) cells. Compared to FMS, CFS/ME exhibits greater systemic immune activation and more severe mitochondrial impairment, correlating with profound fatigue and cognitive decline. IBS, on the other hand, shows immune activation localized to the gastrointestinal tract, emphasizing the gut-brain axis. These findings highlight both shared and syndrome-specific immune features. To better reflect their systemic and immunological complexity, this review refers to these conditions collectively as chronic multisystem immune-related disorders (CMIRDs). The evidence supports the development of biomarker-based diagnostics and personalized immunomodulatory therapies. A multidisciplinary approach that integrates immunology and neurology is essential to improve outcomes for patients with FMS and related disorders.

Unraveling the connection: M2 macrophage polarization and cancer metabolism

Cancer remains one of the leading causes of morbidity and mortality globally, driven by genetic alterations, uncontrolled cell proliferation, and metabolic reprogramming. The tumor microenvironment (TME) is a highly dynamic and heterogeneous system composed of tumor cells, immune cells, stromal cells, and extracellular matrix (ECM) components, which influence cancer progression. Tumor-associated macrophages (TAMs), especially those polarized into the M2 phenotype, play a critical role in modulating this environment. M2 macrophages promote tumor progression through mechanisms such as immune suppression, angiogenesis, and metastasis. This polarization is heavily influenced by the altered metabolic landscape of tumors, where the Warburg effect leads to excessive lactate production, which in turn drives M2 polarization through G protein-coupled receptor 132 (GPR132). M2 macrophages secrete cytokines like IL-10, transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF), which contribute to immune escape, tumor growth, and metastasis. The metabolic shifts within TAMs, especially the transition from oxidative phosphorylation to glycolysis, further support the pro-tumoral functions of these cells. This review explores the intricate relationship between M2 macrophage polarization bias, tumor metabolism, and the resulting impact on cancer progression, highlighting the potential of targeting these pathways for therapeutic strategies. The findings suggest that M2 macrophage polarization could serve as a key prognostic factor for cancer outcomes and provide a basis for future research into therapeutic interventions that target macrophage polarization and the tumor metabolic milieu.

The dual promise of oncolytic viruses: selective targeting and therapeutic enhancement in cancer treatment

Oncolytic virotherapy (OVT) employs genetically engineered or naturally occurring viruses to selectively replicate within tumor cells, leading to direct lysis and induction of systemic anti-tumor immune responses. This dual mechanism distinguishes OVT from conventional therapies and positions it as a promising candidate in precision oncology. This review synthesizes recent advancements in understanding the molecular mechanisms underlying OVT efficacy, including viral entry, replication kinetics, immunogenic cell death, and modulation of the tumor microenvironment. We highlight innovations in viral engineering, such as promoter targeting, microRNA control, and immune-modulatory gene insertions that enhance tumor specificity and therapeutic safety. Clinically, OVT has shown measurable benefits in various solid tumors, with several viruses, such as talimogene laherparepvec, entering regulatory approval and others progressing through late-phase clinical trials. When combined with immune checkpoint inhibitors, OVT has demonstrated synergistic effects by improving antigen presentation and reversing immunosuppressive signaling. Integration with targeted therapies and nanotechnology-based delivery systems has further refined viral biodistribution and pharmacodynamics. However, therapeutic resistance, immune clearance, stromal barriers, and heterogeneous tumor responses remain key limitations. Overcoming these challenges requires optimized delivery routes, predictive biomarkers, and combination strategies tailored to immune and genetic tumor profiles. As OVT evolves from proof-of-concept to a platform-based therapeutic strategy, its integration into multimodal cancer treatment protocols will depend on refined bridge oncolytic activity with durable immunotherapy effects.

Advancements in viral vaccine development: from traditional to modern approaches

Advancements in viral vaccine development have revolutionized public health by reducing the burden of infectious diseases worldwide. The development of vaccinology started with Jenner’s smallpox vaccine and Salk’s polio vaccine among other live attenuated and inactivated vaccines before shifting to modern platforms that include subunit, protein-based, and viral vector vaccines as well as messenger RNA (m-RNA) vaccines. Subunit and protein-based vaccines are the ones that protect specific subpopulations and contain low risks; reverse vaccinology, built on genome sequencing and using computational methods for identification of the antigens, helps to cut the time for vaccination development. The COVID-19 experience by itself has shown the feasibility of faster and easily scalable m-RNA development that provides a very strong immunogenicity and safety profile. These advancements are crucial in the fight against new and resurging pathogens, for example, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV), and influenza. They allow the creation of vaccines for highly mutable pathogens or those that evolve strategies to avoid the immune system. Truly innovational approaches in delivering vaccines are lipid nanoparticles, microneedle patches, and thermostability that improve the stability, accessibility, and administration of vaccines in low- and middle-income countries (LMICs). Furthermore, computational immunology, artificial intelligence, and bioinformatics are involved in creating precision vaccines that are likely to suit different populations in society. This review presents solutions to critical barriers including vaccine refusal among the population and unequal distribution systems and transportation requirements along with clinical trial gender bias. Recent strategies employing nanotechnology-based delivery methods and universal vaccines receive assessment regarding their solutions to present challenges. The need for joint public-private collaborations combined with strong health programs and systematic research investments stands essential for developing extensive scalable vaccination strategies. These findings present a detailed guide for improving both the effectiveness and accessibility of vaccines as well as readiness against current and future viral infections.

Exploring immunotherapeutic strategies for bacterial and viral diseases

The global socioeconomic and health impacts of microbial diseases cannot be overemphasized. The emergence of the coronavirus in 2019 and the ongoing threat of infectious diseases, such as HIV/AIDS, tuberculosis, and hepatitis, remind us of the impact these infections have on economic stability and global health. Gaps in the treatment of microbial infections and their contribution to increased mortality necessitate holistic and long-term solutions, as opposed to antibiotics, which were previously relied upon. Immunotherapy is becoming increasingly promising for the treatment of microbial infections. This study reviews recent advances in immunotherapeutic strategies, particularly cytokine-based therapies, adoptive cell therapy, monoclonal antibodies, and immune checkpoint inhibitors, for the control of antimicrobial resistance. New inventive approaches, such as chimeric antigen receptor T cell therapy and mucosal-associated invariant T cells, have been discussed in the context of bacterial and viral infections, highlighting promising results from clinical trials and addressing the challenges of toxicity, immune evasion, and therapy resistance that are inherent in these diseases. Future priorities include optimizing combination therapies and exploring new immunomodulatory targets to improve the effectiveness of these interventions in treating antimicrobial resistance and other infectious diseases.

Harnessing monocyte-derived dendritic cells for evaluating T cell response by mixed leukocyte reaction

The mixed leukocyte reaction (MLR) is a pivotal in vitro assay for evaluating T-cell responses stimulated by allogeneic antigen-presenting cells (APCs). Dendritic cells (DCs) are the most efficient stimulatory cells. However, the scarcity of circulating DCs in peripheral blood limits their isolation for research or clinical use. In contrast, monocytes, which are abundant and easily accessible, can be differentiated into monocyte-derived DCs (moDCs) in vitro and have emerged as the most practical and efficient stimulatory cells for MLR due to their accessibility and robust allostimulatory capabilities. This review aims to describe the scientific rationale and evidence for using moDCs in MLR assays to assess T-cell alloreactivity. Its methodology outlines the protocols for experimental, preclinical, and biosafety assays that have demonstrated the practicality of moDCs in evaluating and quantifying the alloresponse of naïve and memory CD4+ and CD8+ T cells, as well as the effects of immunomodulatory factors, immune monitoring, and tolerogenic strategies in the context of transplantation. Additionally, it illustrates how moDC-mediated MLRs have provided critical insights into understanding alloimmunity processes and antigen-specific T-cell responses in cancer immunotherapy, autoimmune diseases, and vaccine development, with potential implications for personalized medicine and immunotherapy optimization. In conclusion, despite ongoing challenges such as standardization and scalability in massive cell production, the current understanding and reproducible results of moDC applications in MLRs highlight their potential to develop innovative strategies focused on immune monitoring.

The neutrophil-to-lymphocyte ratio in aging and immunosenescence In recent years the number of publications reporting the use of the neutrophil/lymphocyte ratio (NLR) in disparate fields of human and veterinary medicine has swelled in the medical literature from less than 50/year in 2010 to 892 in 2019, and this figure has more than doubled up to 1,857 in 2024 [1].

Reflections on immune system lessons for societal resilience

The immune system is a masterclass in balance and adaptation. Its ability to distinguish self from non-self, to tolerate internal diversity, to learn from past encounters, and to respond to environmental cues offers more than just biological insight—it offers a framework for thinking about resilient societies. In this perspective, I reflect on the parallels between immune function and the ways communities withstand adversity, adapt, and rebuild. When the immune system falters—through intolerance, loss of memory, or failure to regulate—it mirrors the kinds of dysfunction we see in divided or unjust societies. By learning from the immune system’s strengths and failures, we may find guidance for healing fractured communities and fostering more cohesive, adaptable, and resilient social systems.

Elevation of cytokines and antibodies in guinea pigs experimentally infected with Tunga penetrans

Prognostic values of sera IL-6/IL-10 and high titration of anti-SSA/Ro and anti-SSB/La autoantibodies in female patients with connective tissue diseases

Immune-checkpoint inhibitor resistance in patients with cancer

The introduction of immune checkpoint inhibitors (ICIs) has transformed the landscape of oncology, offering significant improvements in patient survival and achieving remarkable long-term outcomes. Despite these advances, the therapeutic benefits of ICIs are not universal, and existing biomarkers often fall short in accurately predicting patient responses. A comprehensive understanding of the mechanisms underlying resistance to ICIs is essential for the development of strategies to mitigate these challenges and enhance therapeutic efficacy. This review provides a detailed exploration of the resistance mechanisms associated with ICIs, focusing on the role of the tumor microenvironment and intrinsic tumor cell alterations in mediating both primary and secondary resistance. Furthermore, it evaluates emerging strategies to overcome resistance, including combination therapies and innovative therapeutic approaches. By dissecting the molecular and immunological pathways implicated in ICI resistance, this review aims to highlight novel predictive and prognostic biomarkers and outline optimized therapeutic strategies to maximize the clinical impact of ICIs in cancer management.

Impact of sucrose consumption on inflammatory and immunological parameters in newborn offspring of females mice with gestational diabetes mellitus

Identification of potential DAMPs released by necroptosis in estrogen-receptor positive breast cancer cells and their effect on macrophage differentiation

Human inborn errors of immunity: diagnosis and management

Primary immunodeficiency disease (PID) now known as inborn errors of immunity (IEI) is genetic disorder(s) that impair the immune system. IEI is a heterogeneous group of diseases of more than 485 lifelong genetic disorders mainly due to intrinsic defect(s) in human immune system. Adults, children, and neonates can be affected by IEI diseases. The first IEI defects were reported in the 1950s, but Bruton’s use of immunoglobulin in 1952 to treat an 8-year-old boy suffering from pneumonia and other bacterial sino-pulmonary infections brought the PID or IEI and associated diseases into limelight. This review will focus on a general description of IEI (history, epidemiology, pathophysiology, and diagnosis), inborn errors of metabolism, and the management (cure or therapy) of IEI diseases.

Macrophages in the pathogenesis of monogenic muscular dystrophies: inflammation, fibrosis, and therapeutic implications

Monogenic muscular dystrophies (MDs), such as Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD), are characterized by chronic inflammation, progressive fibrosis, and impaired muscle regeneration. Central to these pathological processes are macrophages, which exhibit dynamic polarization states that influence the dystrophic microenvironment. In early disease stages, macrophages support tissue repair and regeneration, but chronic inflammation skews their activity toward pro-fibrotic phenotypes, driving excessive extracellular matrix (ECM) deposition and muscle dysfunction. Macrophages also interact with other immune cells, such as T cells and neutrophils, and non-immune cells, including fibroblasts and satellite cells, to regulate inflammatory and fibrotic responses. These interactions establish a dysregulated immune environment that exacerbates muscle damage and impairs effective regeneration. Preclinical studies using the mdx mouse model of DMD highlight the critical role of macrophages in sustaining inflammation and fibrosis, particularly through transforming growth factor-beta (TGF-β) signaling and fibro-adipogenic progenitor (FAP) activation. Therapeutically, targeting macrophages offers significant potential to mitigate disease progression. Strategies include modulating macrophage polarization toward a pro-regenerative M2 phenotype, inhibiting macrophage recruitment via chemokine signaling, and reprogramming macrophage metabolism to support oxidative phosphorylation and mitochondrial function. Additionally, anti-fibrotic interventions targeting TGF-β signaling or macrophage-FAP crosstalk have shown promise in reducing ECM deposition and preserving muscle architecture. In this review, we curate relevant studies and provide insights into the molecular mechanisms governing macrophage behavior in dystrophic muscle. Herein, we discuss how emerging therapeutic strategies targeting macrophage-mediated pathways can be leveraged to mitigate inflammation and fibrosis, enhance muscle regeneration, and improve clinical outcomes.

Predominant pro-inflammatory environment in mid-gestation pregnant women with history of recurrent pregnancy loss: a South Indian study

Neoantigen vaccines: advancing personalized cancer immunotherapy

Neoantigen vaccines are a promising strategy in cancer immunotherapy that leverage tumor-specific mutations to elicit targeted immune responses. Although they have considerable potential, development challenges related to antigen prediction accuracy, manufacturing complexity, and scalability remain key obstacles to their widespread clinical use. This literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases to identify relevant studies. Keywords included “neoantigen vaccines,” “personalized cancer immunotherapy,” “tumor heterogeneity,” “bioinformatics pipelines,” and “prediction algorithms”. Clinical trial data were sourced from ClinicalTrials.gov, Trialtrove, and other publicly available registries. Eligible studies included peer-reviewed research articles, systematic reviews, and clinical trials focusing on neoantigen vaccine development, bioinformatic strategies, and immunotherapy. Tumor heterogeneity and clonal evolution significantly impact vaccine efficacy, necessitating multi-epitope targeting and adaptive vaccine design. Current neoantigen prediction algorithms suffer from high false-positive and false-negative rates, requiring further integration with multi-omics data and machine learning to enhance accuracy. Manufacturing remains complex, time-intensive, and costly, necessitating advancements in standardization and automation. Combination therapies, such as immune checkpoint inhibitors and adoptive cell therapies, counteract the immunosuppressive tumor microenvironment, improving treatment outcomes. Neoantigen vaccines hold great potential for personalized cancer therapy but require advancements in bioinformatics, manufacturing scalability, and immunomodulatory strategies to enhance clinical efficacy. Continued research and interdisciplinary collaboration are essential for refining clinical applications.

Diets for inflammatory bowel disease: impact on microbiome and immunomodulatory microbial metabolites

Diet plays a complex role in the management of inflammatory bowel disease (IBD), significantly influencing the microbiome and metabolome. Three key metabolites implicated in IBD are short chain fatty acids, bile acids and tryptophan, all of which can be modulated through diet. This study analyses the impact of various diets on these metabolites. Despite the anti-inflammatory effects of short chain fatty acids, their levels do not increase during successful remission with exclusive enteral nutrition. Additionally, changes in tryptophan and bile acids are non-specific across different diets, suggesting these metabolic shifts are secondary to dietary efficacy in IBD. Dietary therapies vary in efficacy across individuals, as the established microbiome may not produce the desired metabolites. This variability is further compounded by differences in immune responses influenced by genetic factors and disease duration. Furthermore, inflammation and symptom resolution do not always coincide, revealing a discrepancy in dietary impacts on IBD. These limitations highlight the need for a deeper understanding of the interconnectedness of disease heterogeneity, dietary effects, the microbiome, and their influence on the mucosal immune system to develop more personalised dietary therapies. While no single diet is universally effective for all IBD patients, future research should focus on establishing a more rigid definition of dietary interventions for IBD and their long-term effects on clinical outcomes.

Role of ZEB1 in immune response, inflammation and membrane remodeling during neoplasia

Immune response, inflammation, and lipid metabolism have important effects on cancer development and progression. Several proteins in tumoral cells and/or tumor microenvironment are involved in any of these processes, whereas some of them participate in all three, such as the zinc finger E-box-binding homeobox 1 (ZEB1) protein. This protein has been proposed to have an important role in invasion and metastasis of cancer cells, as well as to be involved in malignant transformation and resistance to cancer treatments. So, in this study, we present the participation of ZEB1 in immune, inflammatory, and membrane remodeling (lipid metabolism) processes, as well as its interaction with proteins that participate in them. Due to the importance of ZEB1 in cancer progression, it may be a potential biomarker of cancer prognosis and a target for the development of new cancer therapies.