3170 - Dissecting Cellular Dynamics Following Radiation-Induced Lung Injury via Single-Cell RNA Sequencing
Presenter(s)
W. Yang1, S. Yue1, T. Lei1, C. Liu2, and Q. Hu1; 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China, 2Department of Radiation Oncology, Peking University First Hospital, Beijing, China
Purpose/Objective(s): Radiation-induced lung injury (RILI) is one of the primary limiting factors of thoracic irradiation, as it can induce acute pneumonitis and pulmonary fibrosis. The prevention and treatment of lung injury are essential for patient prognosis. This study aims to investigate the differences in the microenvironment before and after radiation-induced lung injury.
Materials/Methods: We included and analyzed single-cell RNA sequencing data of 99,016 cells from 6 non-radiation control samples and 11 samples collected from mice at 1 to 5 months post-radiation. Dimensionality reduction and clustering analyses were employed to identify and compare the compositional and characteristic differences among immune cells, tumor cells, and other cellular populations before and after radiotherapy.
Results: The study identified that post-radiation tissues exhibited a higher prevalence of immune cell subpopulations, including exhausted CD4+ T cells, regulatory T cells (Tregs), interstitial macrophages (IMs), conventional dendritic cells (cDCs) and inflammatory fibroblasts. In contrast, pre-radiation tissues were enriched with Th2 cells and alveolar macrophages(AMs). Further investigation into the temporal cellular distribution before and after radiotherapy demonstrated that myofibroblasts initially decreased immediately following radiotherapy but subsequently increased gradually over time, a pattern closely associated with the progression of pulmonary fibrosis. Concurrently, Tregs and IMs showed progressive enrichment over time. Post-radiotherapy, Tregs upregulated pathways related to the negative regulation of immune response and myeloid cell differentiation. Additionally, further research identified that the enrichment of IMs in post-radiation tissues may be linked to the upregulation of Ccl2 and Ifi27l2a.
Conclusion: Single-cell analysis has revealed the diverse variations in the microenvironmental components associated with radiation-induced lung injury, suggesting that modulating immune cell activity and the microenvironment may provide novel approaches to preventing and treating radiation-induced lung injury.