Radiation-induced oral mucositis as an immune hub: from innate immune sensing to adaptive immune dysregulation

Radiation-induced oral mucositis (RIOM) has traditionally been viewed as a cytotoxic injury to rapidly proliferating epithelial cells caused by radiotherapy. Recent studies have revealed that RIOM is fundamentally a pivotal radiotherapy-triggered, damage signal-driven dysregulation event of local and systemic immune homeostasis. The severity of RIOM dynamically and directly affects patients' oral health-related quality of life (OHRQoL), serving as an intuitive reflection of their local immune-inflammatory status. Key immunological events include the release of unique damage-associated molecular patterns (DAMPs) by radiotherapy, which actively initiate and shape the intrinsic immune recognition program; functional shifts and imbalances in critical immune subsets such as neutrophils, macrophages, and T cells, forming the core circuitry of sustained injury and impaired repair; and the chronic immune microenvironment, which not only drives local pathology profoundly influencing systemic antitumor immune responses and long-term complications. This review aims to establish the emerging interdisciplinary framework of radioimmunomucosology, providing a novel perspective for optimizing comprehensive cancer therapy. Additionally, systematic studies have revealed that radiotherapy induces predictable ecological dysbiosis in the oral microbiome, characterized by depletion of commensal bacteria and expansion of opportunistic pathogens. This suggests that RIOM involves radiation-triggered disruption or confrontation between host immunity and commensal microorganisms.