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Peer-reviewedCC BY 4.0Frontiers in Immunology

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

  • Xiaoguang Xue1,2
  • Shenghong Qiu1,2
  • Jianxiao Zheng1,2
  • Yilin Kong1,2
  • Lei Gao1,2
  • Wenting Zhan1,2
  • Weiwei Guo1,2
  • Jixin Chen1,2
  • Longmei Li1,2
  1. 1Department of Radiotherapy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
  2. 2State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{xue2026radiationinduced,
  title = {{Radiation-induced oral mucositis as an immune hub: from innate immune sensing to adaptive immune dysregulation}},
  author = {Xiaoguang Xue and Shenghong Qiu and Jianxiao Zheng and Yilin Kong and Lei Gao and Wenting Zhan and Weiwei Guo and Jixin Chen and Longmei Li},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1905406},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1905406/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Radiation-induced oral mucositis as an immune hub: from innate immune sensing to adaptive immune dysregulation
AU  - Xiaoguang Xue
AU  - Shenghong Qiu
AU  - Jianxiao Zheng
AU  - Yilin Kong
AU  - Lei Gao
AU  - Wenting Zhan
AU  - Weiwei Guo
AU  - Jixin Chen
AU  - Longmei Li
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1905406
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1905406/full
AB  - 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.
SN  - 1664-3224
ER  -