MDA-7/IL-24在甲状腺癌中与Thomsen-Friendreich抗体免疫治疗的协同作用机制研究

Thomsen-Friendreich抗原（TF-Ag）已被证实可作为甲状腺癌(Thyroid Cancer,TC)有效诊治靶点。TF-Ag特异性抗体（TF-Ab）与细胞因子黑色素瘤分化相关基因-7（MDA-7/IL-24)均已在多种肿瘤中被证实存在显著抗癌作用。本课题组前期研究发现TF-Ab免疫治疗可有效中和TF-Ag并在不同TC细胞株上发挥差异抑癌效应，然而在不同TC细胞株中TF-Ab免疫治疗均可有效促进MDA-7/IL-24表达。因此，本课题组推测TF-Ag在不同TC细胞株上与TF-Ab存在差异结合位点，而TF-Ab干预可影响MDA-7/IL-24的转录调控，MDA-7/IL-24有望作为TF-Ab免疫治疗的有效协同手段。本项目拟通过探索出TF-Ab干预后调控MDA-7/IL-24的上游转录因子，并深入探索二者之间可能的协同作用机制，以期为今后TC的防治提供新的治疗策略。

Thomsen-Friendreich antigen (TF-Ag) has been shown to be an effective target for the diagnosis and treatment of Thyroid Cancer (TC). Both TF-Ag specific antibody (TF-Ab) and cytokine melanoma differentiation related gene-7 (MDA-7/IL-24) have been shown to have significant anticancer effects in a variety of tumors. Our previous study found that TF-Ab immunotherapy can effectively neutralize TF-Ag and exert different tumor suppressive effects on different TC cell lines. However, TF-Ab immunotherapy can effectively promote the expression of MDA-7/IL-24 in different TC cell lines. Therefore, our research group speculated that TF-Ag had different binding sites with TF-Ab in different TC cell lines, and TF-Ab intervention could affect the transcriptional regulation of MDA-7/IL-24, and MDA-7/IL-24 is expected to be an effective synergistic means of TF-Ab immunotherapy. This project aims to explore the upstream transcription factors that regulate MDA-7/IL-24 after TF-Ab intervention, and further explore the possible synergistic mechanism between them, so as to provide new therapeutic strategies for the prevention and treatment of TC in the future.