Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.
Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.
复制标题
DOI：
10.4110/in.2016.16.1.75
复制
发表时间：
2016-02
期刊：
影响因子：
6
通讯作者：
Lee H
中科院分区：
文献类型：
--
作者：
Son KJ;Choi KR;Lee SJ;Lee H
癌症是全球发病率和死亡率的主要原因之一;因此，需要发现具有改善的功效和安全性的新治疗模块。免疫（细胞）治疗是治疗难治性癌症的一种有前途的治疗策略。已经报道了某些化疗剂在诱导免疫原性肿瘤细胞死亡从而促进癌症根除中的有效性。人参皂苷Rg 3是具有抗肿瘤和免疫调节活性的人参皂苷。在这项研究中，我们用Rg 3处理肿瘤细胞，以验证诱导免疫原性肿瘤细胞死亡在抗肿瘤治疗中的意义，特别是在基于DC的免疫治疗中。Rg 3通过诱导细胞凋亡杀死免疫原性（B16 F10黑色素瘤细胞）和非免疫原性（LLC：刘易斯肺癌细胞）肿瘤细胞。免疫原性死亡标志物，包括钙网蛋白和热休克蛋白的表面表达和相关基因的转录增加Rg 3死亡肿瘤。钙网蛋白表达的增加与树突状细胞（DC）对垂死肿瘤细胞的摄取直接相关：Rg 3治疗组中CRT+ CD 11 c+细胞的比例增加。有趣的是，通过免疫原性细胞死亡而死亡的肿瘤细胞分泌IFN-γ，一种在T细胞中具有抗肿瘤活性的效应分子。沿着Rg 3诱导的促血管生成（TNF-α）和免疫抑制细胞因子（TGF-β）分泌的抑制，来自Rg 3处理的肿瘤细胞的IFN-γ产生也可能指示Rg 3作为有效的抗癌免疫策略。数据清楚地表明，Rg 3诱导的免疫原性肿瘤细胞死亡是由于其细胞毒性作用及其诱导DC功能的能力。这表明Rg 3可能是一种有效的免疫策略。
Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT+ CD11c+ cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.