Frontiers in Immunology

Background Inborn errors of immunity (IEI) predispose patients to malignancy, particularly lymphoma, but data on diagnostic sequence and outcomes are limited. Methods We retrospectively analyzed IEI-associated malignancies diagnosed at a single center between January 2004 and December 2025. Results Among 1,668 patients with IEI, 67 (4.0%) developed malignancy. Median ages at IEI and malignancy di…

Background Tertiary lymphoid structures (TLSs) are key immune niches involved in antitumor immunity. However, their functional impact depends on spatial localization, maturation status, and cellular composition within the tumor immune microenvironment (TIME). Despite the recognized role of Helicobacter pylori ( H. pylori ) in gastric carcinogenesis and immune modulation, its influence on TLS arch…

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus marked by immune complex deposition and tissue-specific inflammation. Advances in single-cell transcriptomics and high-dimensional immune profiling have revealed that CD8 + T cells form a highly heterogeneous and compartment-dependent landscape across peripheral blood, kidney, and urine. This review aims to delineate h…

Circadian rhythms, an endogenous timing system that enables organisms to adapt to Earth’s rotation, profoundly regulate fundamental physiological processes including cellular metabolism, hormone secretion, and immune surveillance. Recent advances have revealed that circadian disruption drives tumor initiation and progression, with its modulatory role in tumor immunity serving as a pivotal link be…

Background Sepsis poses significant challenges in early detection and treatment due to its heterogeneous nature and overlaps with other conditions, such as pneumonia. Identifying reliable biomarkers is crucial for intervention and outcomes. Methods A total of 190 adults, aged 18 years and above, categorized into four groups: sepsis (n=50), pneumonia (n=53), pneumonia with sepsis (n=34), and healt…

Insects are the most diverse group of animals in nature, occupying nearly every ecological niche and playing central roles as pollinators, pests, and disease vectors. Despite this vast diversity, insects rely on a set of conserved yet evolutionarily adaptable immune pathways to defend against pathogens. Early studies in insect immunity have laid the foundation for human immunology, and recent adv…

Introduction Porcine tonsils are follicle-rich secondary lymphoid organs positioned at the oropharyngeal interface. In pigs, a major livestock species, they serve as a primary barrier against inhaled and ingested pathogens and play a central role in mucosal immunity. Despite their importance as a point of entry and as a reservoir for numerous pathogens, the cellular landscape driving tonsillar im…

Objective Resveratrol is a dietary polyphenol found in grapes, peanuts, and berries, with reported anti-inflammatory, immunomodulatory, barrier-protective, and microbiota-regulating properties. Functional dyspepsia (FD) is associated with duodenal immune dysregulation, epithelial barrier impairment, and microbial imbalance, suggesting an active mucosal microenvironment. This study therefore exami…

Osteoarthritis (OA) is a whole-joint disease in which mechanical exposure and low-grade sterile inflammation interact, but their coexistence does not by itself explain why a normally adaptive response becomes self-sustaining. This Mini Review therefore focuses on a narrower question: how do specific loading conditions push joint-resident cells from reversible mechanoadaptation into persistent inn…

While radiotherapy excels at local tumor control, it seldom orchestrates durable systemic immunity in the context of metastatic disease. The abscopal effect, the regression of non-irradiated distant lesions following focal irradiation, remains a clinical rarity rather than a predictable or robust consequence of monotherapeutic radiotherapy. Clinical manifestations of this phenomenon predominantly…

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet durable benefit remains limited to selected patients. Established biomarkers, including PD-L1 expression, tumor mutational burden, and microsatellite instability, remain predominantly tumor-centered and incompletely capture inter-individual variability. In this Perspective, we highlight systemic host physiology as an under…

Adult human skin healing is predominantly characterized by fibrosis rather than true regeneration, despite the conserved regenerative principles observed in fetal wound healing, liver regeneration, and other biological systems. Historical and contemporary observations in skin allotransplantation, including studies describing the differential behavior of the epidermis and dermis and recent experie…

Traditionally associated with Th17-mediated pathways, palmoplantar pustulosis (PPP) is a persistent inflammatory dermatosis limited to the palms and soles. However, therapeutic responses to IL-17/IL-23 suppression are often limited, indicating significant immunological heterogeneity. There is growing evidence that type 2-associated immunological pathways may have a role in the persistence of dise…

Graves’ disease (GD) is an autoimmune disorder characterized by the production of stimulatory autoantibodies against the thyrotropin receptor, leading to hyperthyroidism and diffuse goiter. The most frequent extrathyroidal manifestation is Graves’ ophthalmopathy (GO), also known as thyroid eye disease (TED), which is responsible for significant morbidity due to orbital inflammation, tissue remode…

Background Individuals with attention-deficit/hyperactivity disorder (ADHD) show an elevated incidence of non-small cell lung cancer (NSCLC), usually attributed to smoking. Innate immune activation and chronic inflammation are implicated in both, yet whether shared germline genetics include a component statistically independent of the measured current-smoking phenotype, and whether that liability…

Mitochondrial DNA (mtDNA) is increasingly recognized as an active driver of immune dysregulation in systemic lupus erythematosus (SLE), yet most existing reviews treat it as a single damage signal rather than a multifunctional pathological mediator. This review presents an integrated framework examining mtDNA as a central hub linking mitochondrial dysfunction to systemic autoimmunity. We conducte…

Endothelial dysfunction and mitochondrial impairment are key early events in atherogenesis and exhibit sex-specific patterns. Resveratrol and metformin are cardiometabolic modulators with antioxidative and mitochondrial effects, but their sex-dependent actions in human iPSC-derived endothelial cells (iPSC-EC) remain unclear. iPSC-EC generated from peripheral blood mononuclear cells of six male an…

Secondary lower-extremity lymphedema has long been regarded primarily as a disorder of impaired lymphatic fluid return. However, growing evidence indicates that its core pathology is a lymph stasis-driven immune–stromal remodeling process characterized by chronic inflammation, extracellular matrix remodeling, and progressive adipose deposition, which gradually reduces limb reversibility as the di…

Tuberculosis (TB), caused by Mycobacterium tuberculosis , continues to be a major health issue worldwide. Granulomas are characteristic lesions of TB, functioning both as host defense structures and as sites where bacteria persist. To explore immune features associated with bacterial control versus disease progression, we examined the cellular composition and spatial arrangement of non-necrotic g…

Background The clinical manifestations of anti-synthetase syndrome-associated interstitial lung disease (ASyS-ILD) are highly heterogeneous, and the mechanisms underlying its development and progression remain poorly understood. This study aimed to identify distinct clinical phenotypes of ASyS-ILD and clusters associated with progressive pulmonary fibrosis (PPF) using unsupervised cluster analysi…