Abstract: Cancer is a leading cause of death worldwide. In cancer treatment, over 65% of patients require radiotherapy either alone or in combination with other therapies. Radiation-induced lung injury is a major complication during chest radiotherapy, involving a complex pathological process that spans multiple stages, primarily divided into radiation pneumonitis and radiation-induced pulmonary fibrosis. Radiation pneumonitis is the early stage of fibrosis, characterized by acute pulmonary tissue inflammation. Radiation-induced pulmonary fibrosis is the late stage of radiation-induced lung injury, characterized by the abnormal activation of myofibroblasts and excessive accumulation of extracellular matrix (ECM). Radiation-induced pulmonary fibrosis limits the radiation dose required to effectively kill tumor cells and is a major obstacle to improving the cure rate and quality of life for lung cancer patients. Although the exact mechanisms are not yet clear, a growing body of evidence suggests that, at the genetic level, ionizing radiation-induced DNA damage and epithelial-mesenchymal transition (EMT) directly affect radiation-induced pulmonary fibrosis; at the cellular level, multiple cell types and cytokines play a crucial role. Damage and differentiation of alveolar epithelial cells and vascular endothelial cells trigger the aggregation of inflammatory and fibrotic cells, imbalance of Th1/Th2 lymphocyte ratios, polarization and recruitment of macrophages, and the formation of myofibroblasts, all of which play significant roles. This article reviews the cells, signaling pathways, and gene regulation involved in the process of radiation-induced lung injury, aiming to explore the understanding of radiation-induced pulmonary fibrosis. It is hoped that this will clarify the key molecular mediators that initiate and control the radiation-induced pulmonary fibrosis response, early diagnosis, and therapeutic targets, significantly improving the efficacy of radiotherapy for lung cancer patients and reducing the side effects of radiotherapy for patients with thoracic tumors.
Key words: radiation-induced lung injury; radiation-induced pulmonary fibrosis; extracellular matrix; immune microenvironment; cytokines
（Acta Laser Biology Sinica, 2025, 34(4): 289-295）
PDF(2176 KB)
