Abstract:Background and Aims Papillary thyroid carcinoma (PTC), the most common type of thyroid cancer, has been rapidly increasing in incidence worldwide, posing a serious threat to individual health and public healthcare systems. Exposure to low-to-moderate doses of ionizing radiation is more relevant to the daily lives of the general population and, therefore, raises greater public health concerns. It has also been widely recognized as a potential factor in immune system remodeling. This study was conducted to investigate the impact of low-to-moderate dose ionizing radiation on the tumor immune microenvironment of PTC, aiming to reveal the potential hazards of such radiation exposure in PTC patients.Methods Two datasets (GSE29265 and GSE35570) containing RNA-seq data and corresponding clinical information were retrieved and downloaded from the GEO database. These datasets included thyroid cancer samples from patients exposed to ionizing radiation due to the Chernobyl disaster, as well as sporadic thyroid cancer cases. After data cleaning, merging, batch effect correction, differential gene expression analysis, functional enrichment analysis, immune cell infiltration analysis, and tumor microenvironment analysis were performed using R language.Results In tumor samples, the radiation-exposed group exhibited significant differential gene expression compared to the sporadic group, with three genes upregulated and 27 genes downregulated. These differentially expressed genes were primarily enriched in biological functions closely related to immune responses, including chemokine activity, immune cell chemotaxis, and tumor immunity. Immune cell infiltration analysis indicated that radiation exposure had a limited impact on immune cell infiltration in normal samples. However, in tumor samples, the immune and ESTIMATE scores were significantly lower in the radiation-exposed group than in the sporadic group. Further analysis revealed that total T cells, CD4+ T cells, CD8+ T cells, B cells, and cytotoxic lymphocytes exhibited significantly lower infiltration levels in the tumor microenvironment of the radiation-exposed group than the sporadic group.Conclusion Although low-to-moderate dose ionizing radiation has a relatively minor impact on normal thyroid tissue, it significantly reduces the infiltration of various immune cell subtypes in the PTC tumor microenvironment. This reduction in immune infiltration may have important implications for disease progression.