放射性碘-125粒子植入下调MDSCs功能抑制肺癌的分子机制研究

放射性碘-125粒子植入治疗作为肿瘤近距离治疗方式之一，是早期前列腺癌的标准治疗之一，同时也是美国国立综合癌症网络（NCCN）指南推荐的多种癌的挽救性治疗手段。研究已证实骨髓来源的抑制性细胞（MDSC）可加快肿瘤进程及促进转移。前期结果显示在肺癌患者及小鼠肺癌模型中随着肿瘤分期的增加MDSC数量及频率显著升高。使用中和抗体清除小鼠MDSC后，肿瘤荷载显著减小，肿瘤进程显著延长。而经粒子治疗后MDSC的PD-L1和TGF-β表达显著降低，而CD8+效应T细胞显著升高，且分选纯化的MDSC对T细胞的抑制功能显著降低。基于此我们假设“粒子治疗通过抑制MDSC的功能进而抑制肿瘤进程”。课题将围绕粒子治疗对MDSC表型、数量及功能的影响，以及相关机制展开研究。将粒子治疗与靶向MDSC的免疫治疗联合应用将会有非常重要的前景。因此，探讨粒子治疗对MDSC功能的影响及相关机制将具有十分重要的意义。

Radioactive iodine-125 seed implantation is one of the standard treatments for early prostate cancer and is recommended by the national comprehensive cancer network (NCCN) guidelines as a salvage treatment for many cancers. Myeloid-derived suppressor cells (MDSC) have been shown to accelerate tumor progression and promote metastasis. Our preliminary results showed that the number and frequency of MDSC increased significantly with the increase of tumor stage in lung cancer patients and mouse lung cancer models. After depleting MDSC in mice with neutralization antibody, tumor burden was significantly reduced and tumor progression was significantly prolonged. However, PD-L1 and TGF-beta expression of MDSC were significantly decreased after I-125 therapy, while CD8+ effector T cells were significantly increased, and the inhibitory function of purified MDSC on T cells was significantly reduced. Based on this, we hypothesized that “Radioactive iodine-125 seed implantation inhibits tumor progression by inhibiting the function of MDSC". This project will focus on the effect of I-125 therapy on the phenotype, quantity and function of MDSC, as well as related mechanisms. The combination of I-125 therapy and MDSC-targeted immunotherapy has important prospects. Therefore, it is of great significance to explore the effect of radioactive I-125 seed implantation on MDSC function and its related mechanisms.