纳秒脉冲电场(nsPEF)消融使肿瘤细胞凋亡，同时可通过免疫效应抑制肿瘤远处转移。超顺磁性氧化铁(SPIO)纳米粒子能诱导巨噬细胞产生抗肿瘤非特异性免疫。我们前期研究发现nsPEF局部消融肝癌后，可产生局部和全身免疫反应，消融区域周围巨噬细胞增加并吞噬肿瘤细胞。本研究拟通过体外实验观察nsPEF和/或SPIO刺激巨噬细胞诱导分化、抗原表位改变、特异性及非特异性免疫反应因子变化；观察nsPEF、SPIO以及诱导后巨噬细胞对肝癌细胞生物学行为及抗原改变的影响。将SPIO纳米粒子经静脉注入nsPEF局部消融后的肝癌荷瘤动物体内，检测nsPEF引起的以肿瘤相关巨噬细胞改变为主的免疫效应及其机制；采用MR活体监测SPIO在肝癌及周围组织分布，验证SPIO抗肿瘤免疫作用；观察二者协同治疗肝癌的效果，明确二者是否具有协同诱导抗肿瘤免疫作用及可能机理，为提高肝癌等恶性肿瘤综合介入治疗效果提供新思路。

Nanosecond pulsed electric field (nsPEF) can cause apoptosis of tumor cell and inhibit distant metastasis of tumor by immunological effect. Superparamagnetic iron oxide (SPIO) nanoparticles can induce macrophages to produce synergistic antitumor immune reaction. Our previous study indicated that local nsPEF ablation of liver cancer can produce local and systemic immune responses, increase macrophages aggregation around the ablation area and phagocytose tumor cells. This study intends to observe the induction of differentiation, epitope changes, specific and non-specific immunological response factors of macrophages stimulated by nsPEF and/or SPIO in vitro, and to observe the biological behavior and the effects of antigenic changes of hepatocellular carcinoma cells stimulated by nsPEF and induced macrophages. The SPIO nanoparticles are injected intravenously into the tumor-bearing animals after nsPEF ablation, and the immunological effect induced by nsPEF will be mainly detected by tumor-associated macrophage changes. The MR will be used to monitor the distribution of SPIO in liver cancer and surrounding tissues and testify the anti-tumor immunity of SPIO. We intend to observe the effect of both treatments for liver cancer and to determine whether the two treatments have synergistic induction of anti-tumor immunity and its possible mechanism, which will provide new ideas for improving the overall efficacy of comprehensive interventional treatment for hepatocarcinoma and other malignant tumors.