Air pollution is a leading global environmental health risk, responsible for millions of premature deaths worldwide each year. Although traditionally associated with respiratory and cardiovascular diseases, accumulating epidemiological and mechanistic evidence now demonstrates that air pollution acts as a systemic toxicant, contributing to a wide spectrum of pathologies across nearly all major organ systems. These include pulmonary and extrapulmonary malignancies, neurodegenerative disorders, cardiovascular and renal diseases, metabolic dysfunction-associated fatty liver disease, dermatological conditions, and sensory organ impairment. In this comprehensive review, we synthesize large-scale population studies, experimental models, and molecular evidence to define air pollution as a multi-organ pathogenic exposure driven by convergent biological mechanisms. Disease development across organs is driven by shared mechanisms such as oxidative stress, inflammation, epigenetic changes, and extracellular vesicle signaling, while organ-specific exposure pathways determine tissue vulnerability. Importantly, we emphasize that disease risk is not dictated by exposure alone. Genetic susceptibility plays a decisive role in shaping individual responses to air pollution, with polygenic risk scores and functional variants in detoxification, antioxidant, immune, and host-defense pathways modifying exposure–response relationships. Evidence from human cohorts and genetically defined animal models underscores gene–environment interactions as key drivers of interindividual heterogeneity in pollution-related disease. By integrating mechanistic convergence with organ-specific exposure biology and genetic susceptibility, this review reframes air pollution as a systemic driver of chronic disease. We further identify critical knowledge gaps related to real-world multipollutant exposure, biological resilience, and precision prevention, providing a conceptual foundation for targeted interventions and risk stratification in pollution-exposed populations.
Gastrointestinal tumors are characterized by high global incidence and mortality rates. Although immune checkpoint inhibitors (ICIs) have achieved breakthroughs in some of these cancers, their overall response rate remains low. Neoantigen cancer vaccines have emerged as a promising new strategy for immunotherapy in gastrointestinal tumors due to their high specificity and strong immunogenicity. These vaccines effectively activate specific T-cell immunity and can produce synergistic effects when combined with ICIs. Various vaccine platforms offer distinct advantages, and clinical trials have shown encouraging potential in inducing immune responses and extending progression-free survival. Meanwhile, current challenges and future directions cannot be ignored. Key challenges primarily involve the accuracy of neoantigen prediction, tumor heterogeneity, and optimal treatment timing. Future directions include artificial intelligence (AI)-assisted multi-omics screening, the development of universal vaccines, optimization of novel delivery systems, and multimodal combination strategies. These advances are expected to promote the application of neoantigen cancer vaccines in postoperative recurrence prevention and early-stage treatment, ultimately moving toward personalized precision immunotherapy. This article systematically reviews the clinical progress and prospects of neoantigen cancer vaccines in treating gastrointestinal tumors, aiming to provide insights for immunotherapy in this field and offer new perspectives for further optimization of such vaccines.
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a key intracellular pattern recognition receptor that senses bacterial peptidoglycan-conserved motifs, and has long been implicated in initiating immune responses. Loss-of-function mutations in NOD2 have been identified as the strongest genetic risk factor for Crohn’s disease (CD), a primary subtype of inflammatory bowel disease (IBD), underscoring its significance in the gut homeostasis. Recent advancements extend our understanding of NOD2, revealing how gut microbiota variation impacts NOD2 signaling and broadening its pathological significance far beyond CD. This review highlights the transition from focusing on genetic mutations in NOD2 to examining its dynamic regulation by the gut microbiome. This new perspective not only deepens our understanding of NOD2 in diverse health contexts, but also paves the way for innovative therapeutic strategies targeting the gut microbiota–NOD2 axis.
