远隔效应有效改善中晚期肝细胞癌（HCC）的放射治疗，T细胞免疫是介导远隔效应的核心机制。ACER2降解CER生成SPH，SPH磷酸化形成S1P，ACER2是调控SPH、S1P的关键酶。已知SPH有多种抑癌活性；S1P促进T细胞趋化、生存、活化介导抗肿瘤免疫。我们前期研究显示人HCC组织存在ACER2表达下调，放射线照射可在人HCC细胞上调ACER2，过表达ACER2提高SPH可显著增强放射线照射诱导的HCC细胞死亡，并显著提高HCC细胞分泌S1P。S1P是T细胞免疫的增强因子，我们认为ACER2-S1P代谢轴可增强T细胞免疫提高HCC放射治疗的远隔效应，本课题将在细胞及免疫感受态动物水平，探索ACER2介导SPH生成在促进放射治疗杀伤HCC细胞的同时，是否通过增加S1P，促进T细胞的抗肿瘤免疫，激活系统性的肿瘤免疫监视，扩大HCC放射治疗的远隔效应，为改善中晚期HCC的放射治疗提供新思路。

The abscopal effect has been implicated to improve the radiotherapy of advanced hepatocellular carcinoma (HCC). The T cell immunity serves as the core mechanism of abscopal effect. ACER2 degrades CER to produce SPH, SPH can be further phosphorylated into S1P. SPH acts as a tumor suppressor, S1P mediates anticancer immunity by promoting T cell chemotaxis, survival, and activation. Our preliminary data demonstrated that ACER2 expression was down-regulated in human HCC cancer tissues, radiation upregulated ACER2 in human HCC cells, overexpression of ACER2 increased SPH and significantly enhanced radiation-induced HCC cell death and S1P secretion. S1P is a potent enhancer of T cell immunity, we hypothesize that elevation of S1P induced by ACER2 upregulation may improve the abscopal effect of radiotherapy against HCC via enhancing T cell immunity. We will explore the role of ACER2 in promoting abscopal effect of radiotherapy in cells and immune competent animals. While upregulation of ACER2 strengthens the radiation-induced HCC cell death by producing SPH, we will examine whether production of S1P by upregulation of ACER2 would improve the anti-tumor immunity of T cells, thus lighten systemic tumor immune surveillance, and promote the abscopal effect of radiotherapy against HCC. This study will provide new ideas for radiotherapy against advanced HCC.