3162 - Single-Cell Transcriptomics Reveals the Dynamic Changes of Tumor-Infiltrating Immune Cells after Radiation in Oral Squamous Cell Carcinoma
Presenter(s)
F. Xia1,2, H. Zhang1,2, S. Cai1,2, Y. Song1,2, Y. Liu1,2, J. Sui1,3, and Y. Wang1,2; 1College of Medicine, Chongqing University, Chongqing, China, 2Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, Chongqing, China, 3Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing,, Chongqing, China
Purpose/Objective(s): Oral squamous cell carcinoma (OSCC), a prevalent malignancy with rising incidence, relies on radiotherapy as a primary treatment. However, the effects of radiation on the tumor immune microenvironment (TIME) remain underdescribed. Emerging evidence highlights TIME's critical role in tumor progression and therapeutic response, comprising dynamic interactions among immune, neoplastic, and stromal cells. Beyond direct cytocidal effects, radiotherapy potentially modulates therapeutic outcomes by reprogramming TIME components and their functional states. Elucidating radiation-induced TIME modifications is essential for optimizing clinical outcomes in OSCC management.
Materials/Methods: This study utilized a mouse model for in vivo subcutaneous tumor formation experiments. We performed single-cell sequencing analysis on OSCC tissue samples to investigate the effects of radiotherapy on TIME. The samples were divided into control, RT3 (3 days post-radiotherapy), and RT10 (10 days post-radiotherapy). We annotated each cell subpopulation, including immune, dendritic, and non-immune cell types, through quality control and dimensionality reduction clustering analysis. The results demonstrated significant alterations in immune cell composition and infiltration rates at different time points post-radiotherapy.
Results: Our results indicate that radiotherapy significantly alters TIME's cellular composition and function. Specifically, the proportion of epithelial cells decreased significantly 10 days after radiotherapy, while the infiltration of CD8+ T cell populations exhibited distinct variation trends. By further subdividing CD8+ T cells, we found that IFN?-expressing CD8_01 cells significantly increased at 3 days post-radiotherapy but decreased by 10 days. Conversely, CD8_02/04/05/06 cell populations primarily exhibited characteristics of exhausted T cells, showing a decrease at 3 days after radiotherapy but an increase at 10 days. Moreover, the results indicated a significant increase in mDC and cDC2 cell proportions 10 days after radiotherapy. We also subdivided myeloid cells into five subpopulations and found substantial differences in the infiltration rates among the various sample groups. A similar pattern was observed in macrophages, where our analysis revealed significant differences in the expression levels of marker genes among different subpopulations.
Conclusion: This study's results provide new insights into the interactions between radiotherapy and the immune microenvironment, emphasizing the importance of TIME in treatment plans. Further studies will focus on elucidating the synergistic effects of radiotherapy with other immunotherapeutic modalities, especially in combination with immune checkpoint inhibitors. By optimizing the combination of radiotherapy and immunotherapy, we aim to provide more personalized and precise treatment strategies for OSCC patients, ultimately improving their survival.