Immunotherapy: Toward a new era in type 1 diabetes prevention and treatment.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive loss of pancreatic beta cells, leading to insulin deficiency and hyperglycemia. Despite advances in glucose monitoring and automated insulin delivery, these technologies cannot replace the unique metabolic and endocrine functions of endogenous beta cells. Preserving or restoring beta cell function remains the ultimate goal of T1D research.Over the past decades, our understanding of T1D immunopathogenesis has expanded beyond a T-cell-centric view. T1D is now recognized as a complex, heterogeneous disease arising from dynamic interactions among multiple immune populations, including autoreactive CD4⁺ and CD8⁺ T cells, B cells, antigen-presenting cells, innate immune cells such as macrophages and neutrophils, and the beta cells themselves. B cells are increasingly appreciated not only as producers of autoantibodies but also as potent antigen-presenting cells that modulate T-cell activation. Beta cells actively participate in their own demise by expressing stress signals, presenting antigens, and secreting inflammatory mediators that amplify immune attack. The tempo and trajectory of disease progression vary between individuals, reflecting underlying genetic, immunologic, and environmental heterogeneity.Recent breakthroughs, such as the approval of teplizumab to delay clinical onset, demonstrate that immunotherapy can modify disease course. Yet the failure of other interventions in stage 3 diabetes, such as antigen-specific vaccines, highlights the complexity of T1D and the limitations of single-target strategies. These observations underscore the need for precision medicine approaches that consider an individual’s immune landscape, beta cell phenotype, and disease stage.Looking forward, the next generation of T1D immunotherapy may involve:• Beta-cell-centric interventions that enhance stress resilience, promote survival, and reduce immunogenicity. • Neoantigen-targeted strategies to induce antigen-specific tolerance in early disease stages. • Immune checkpoint modulation to restore tolerance without broad immunosuppression. • Combination therapies that simultaneously modulate T cells, B cells, innate immunity, and beta cell resilience. • Biomarker-driven precision medicine, leveraging immune, metabolic, and genetic profiling to tailor therapy to individual patients. • Innovative preclinical models that capture human disease heterogeneity and enable testing of multi-pronged approaches. This research topic seeks contributions that explore the full spectrum of T1D immunopathogenesis and cutting-edge strategies to prevent or halt disease progression, maintain C-peptide production, and ultimately restore immune tolerance. We welcome studies from basic immunology, beta-cell biology, and translational clinical research that interrogate new targets, combination therapies, and patient-tailored approaches.By integrating insights across the immune-beta cell network and embracing the diversity of disease trajectories, the field can move toward personalized, durable, and effective interventions, shaping a future where T1D can be prevented, delayed, or even reversed. Topic editors: Prerak Trivedi, Conny Gysemans Source: https://www.frontiersin.org/research-topics/79452/immunotherapy-toward-a-new-era-in-type-1-diabetes-prevention-and-treatment