Immunological tolerance at the crossroads of autoimmunity and oncology: Mechanisms, plasticity, and therapeutic frontiers

Immunological tolerance underpins the delicate balance between protective immune responses and the prevention of pathological autoimmunity. Failures in tolerance mechanisms can lead to chronic inflammatory and autoimmune conditions, whereas excessive or tumor-induced tolerance can allow cancers to evade immune surveillance. This duality has become increasingly evident with the advent of immunotherapies, where restoring or disrupting tolerance can lead to both transformative clinical responses and immune-related adverse events. This Research Topic seeks to provide a state-of-the-art platform to explore the molecular and cellular mechanisms of tolerance in health and disease, with particular emphasis on how these pathways are modulated in autoimmunity, cancer, and therapeutic interventions. By bridging mechanistic studies and translational insights, the collection aims to advance our understanding of tolerance and its regulation in diverse clinical contexts.We welcome original research, reviews, and perspectives that advance knowledge on the mechanisms and regulation of immune tolerance, particularly in relation to T cell biology and regulatory networks. Areas of focus include:-Microbiome-modulated induction of regulatory T cells (Tregs) and their stability in dynamic microenvironments-Antigen-specific tolerance induction strategies and their therapeutic applications in autoimmunity-Treg plasticity and the implications of functional instability for immune regulation-Tumor immune responses, including how lymphocyte subsets contribute to either anti-tumor activity or tumor-induced immunosuppression within the microenvironment-Immunotherapy in oncology and autoimmunity, with emphasis on checkpoint blockade, adjuvants, and mechanisms underlying immune-related adverse events-Cross-disciplinary approaches (multi-omics, systems immunology, and in vivo modeling) that dissect the microenvironments permissive for tolerance or highlight how tolerance is bypassed in pathological settingsSubmissions should provide mechanistic and conceptual insights into tolerance and regulation rather than focus narrowly on disease-specific treatments. We encourage contributions that link fundamental biology of tolerance mechanisms—such as coinhibitory molecules, tolerogenic drug effects, and microenvironmental cues—to their translational implications in therapy. Studies that explore the consequences of tolerance breakdown in autoimmunity, or conversely, the exploitation of tolerance pathways by tumors, are particularly welcome. Reviews should aim to integrate emerging concepts across tolerance, immune plasticity, and immunotherapy, while original research should demonstrate methodological rigor and, where applicable, validation in relevant experimental or clinical systems.This collection, hosted in the Immunological Tolerance and Regulation section of Frontiers in Immunology, seeks to capture the complexity and therapeutic potential of tolerance biology at the intersection of autoimmunity and oncology. By doing so, it will contribute to shaping future strategies for restoring balance in immune regulation and advancing immunotherapies that improve patient outcomes. The topic editors declare no conflict of interest Topic editors: Maria Perez-Lanzon, Karsten Kretschmer Source: https://www.frontiersin.org/research-topics/76646/immunological-tolerance-at-the-crossroads-of-autoimmunity-and-oncology-mechanisms-plasticity-and-therapeutic-frontiers