超声引导射频消融术对荷肝癌小鼠循环及肿瘤浸润T细胞免疫检查点表达水平影响及其机制的研究

超声引导射频消融（RFA）已成为肝癌重要治疗手段之一，但RFA治疗存在局部复发及远处转移率较高问题。系列研究发现消融后患者体内大部分活化T细胞功能出现耗竭，而免疫检查点（PD-1,Tim-3及CTLA-4）的高表达与T细胞功能耗竭密切相关，这可能与消融后复发转移率高有关，且靶向阻断PD-1/PD-L1单独治疗难以完全逆转机体免疫抑制状态。申请人课题组在前期成功验证荷肝癌小鼠较对照鼠循环及肿瘤浸润T细胞PD-1表达水平明显升高基础上，拟构建双侧背部荷肝癌小鼠模型，并对单侧肿瘤行RFA及联合免疫检查点抑制剂治疗，通过检测分析瘤体及小鼠体内免疫检查点水平的演变及其机制，并结合瘤体超声造影定量及高频弹性超声技术，分析微灌注及形态学改变与分子水平改变相关性，从而为评估RFA对T细胞免疫检查点影响及影像学监测治疗，及将来消融与免疫治疗的临床决策提供实验依据。

Ultrasound-guided radiofrequency ablation (RFA) has become one of the important treatments for liver cancer, but RFA treatment has problems of high rate of local recurrence and distant metastasis. A series of studies have found that most of the activated T cells in the patient's body are depleted after ablation, and the high expression of immune checkpoints (PD-1, Tim-3 and CTLA-4) is closely related to T cell depletion, which may be related to high relapse and metastasis after ablation, and targeted blockade of PD-1 / PD-L1 alone is difficult to completely reverse the immune suppression state of the body. Based on the successful verification of high PD-1 expression level of circulating and tumor-infiltrating T cells bearing the liver cancer mice in the early stage, the applicant's research group plans to build a bilateral back-bearing liver cancer mouse model and perform RFA combined with immune checkpoint inhibitor treatment on unilateral tumor, by analyzing the evolution and mechanism of immune checkpoint levels in tumors and mice, combined with contrast ultrasound quantitative and high-frequency elastic ultrasound technology data, analyze the correlation of microperfusion and morphological changes and the molecular level, and provides an experimental basis for evaluating the impact of RFA on T-cell immune checkpoints and imaging monitoring, as well as future clinical decisions for combination treatment of ablation and immunotherapy.