同济大学学报(医学版)2025,Vol.46Issue(5):663-668,6.DOI:10.12289/j.issn.2097-4345.24505
131I及STING激动剂对甲状腺癌免疫细胞浸润的影响
Effects of 131I and STING agonist on immune cells in thyroid carcinoma
摘要
Abstract
Objective To investigate the effects of 131I and STING agonist on immune cells in thyroid carcinoma in a nude mouse model of thyroid cancer.Methods Thyroid carcinoma transcriptome data downloaded from database TCGA was utilized to generate grouping clustering heat maps demonstrating the infiltration of immune cells in thyroid carcinoma tissue to initially screen the study subjects.The nude mice model of thyroid carcinoma were divided into 4 groups according to intervention methods:0.5 mCi 131I group(intraperitoneal injection),1.0 mCi 131I group(intraperitoneal injection),STING agonist intervention group(peritumoral injection)and blank control group.The FFPE samples were prepared with stripped tumor tissues from the nude mice for HE staining and immunofluorescence experiments.The intensity of immunofluorescence staining was semi-quantitatively analyzed using Image J software.Group differences were compared using one-way analysis of variance,with statistical significance defined as P<0.05.Results The TCGA database included data on immune cell infiltration in thyroid carcinoma samples from 494 patients,encompassing 22 types of immune cells.The CD8+T cells and CD4+T cells exhibited significant differences in infiltration levels within thyroid carcinoma tissues.Compared with the blank control group,the tumor length in both the 1.0 mCi 131I group[(4.86±1.10)mm,P<0.001]and STING agonist group[(4.34±0.44)mm,P<0.001]decreased significantly.Whereas no significant statistic differences was observed in Ki-67 and E-cadherin's relative fluorescence intensity among multiple groups(both P>0.05).The relative fluorescence intensity of CD8+T cells in tumor tissues in the 131I intervention group were both lower than that in the STING agonist group(both P<0.05).Furthermore,there were no statistically significant differences in CD4+T cell or Treg cell immunofluorescence relative fluorescence intensity in both pairwise and multiple group comparisons(all P>0.05).The ratio of CD4+T cells/CD8+T cells in the 1.0 mCi 131I group was 3.90±1.53,which was significantly higher than that in the blank control group(1.14±1.03,P=0.047).There was significant difference in the ratio of CD8+T cells/Treg cells between the 0.5 mCi 131I group and the STING agonist group(P=0.019).Conclusion Both 131I and STING agonists demonstrate inhibitory effects on tumor growth.131I enhances the ratio of CD4+T cells to CD8+T cells,while STING agonists facilitate the differentiation of CD8+T cells into Treg cells.关键词
甲状腺癌/131I/STING激动剂/肿瘤微环境Key words
thyroid carcinoma/131I/STING agonist/tumor microenvironment分类
医药卫生引用本文复制引用
佟君羽,蒋永继,郁霞青,蔡海东,马超,吕中伟..131I及STING激动剂对甲状腺癌免疫细胞浸润的影响[J].同济大学学报(医学版),2025,46(5):663-668,6.基金项目
国家自然科学基金(82202203) (82202203)
上海市第十人民医院"医研融合"专项项目(SYYYRH2025053) (SYYYRH2025053)