Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice
Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice
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DOI：
10.3892/or.2014.3500
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发表时间：
2014-12-01
期刊：
影响因子：
4.2
通讯作者：
Matsubara, Hisahiro
中科院分区：
文献类型：
--
作者：
Qin, Wei;Akutsu, Yasunori;Matsubara, Hisahiro
本研究的目的是评估调制电热热（mEHT）是否可以诱导远位效应，从而增强免疫治疗的抗肿瘤作用。我们使用瘤内树突状细胞（DC）注射和mEHT治疗C3 H/He小鼠接种鳞状细胞癌SCCVII细胞在左腿，我们评估了全身的抗肿瘤作用。每两天或三天检查肿瘤以评估生长抑制。切除肿瘤引流淋巴结以进行CD 3（+）和CD 8（+）细胞的流式细胞术分析，而免疫组织化学用于评估肿瘤中的CD 8、S100和Foxp 3表达。另外，测量来自不同处理组的肿瘤中的GP 96表达。对照组平均肿瘤体积大于其他组。这些结果表明，肿瘤内DC注射和mEHT的联合治疗引起全身抗肿瘤活性。流式细胞术分析显示DC + mEHT治疗组中CD 3+和CD 8+细胞数量较多。肿瘤组织免疫组化显示，DC + mEHT治疗组中CD 8和S100表达更强，而对照组中Foxp 3表达更高。mEHT组GP 96基因表达水平与对照组相比有显著性差异。mEHT可诱导远位效应，并且GP 96的过表达强烈增强了DCs免疫治疗的效果。GP 96被认为是解释远位效应的分子之一。DCs和mEHT的直接瘤内给药可能是未来可行的治疗策略。
The aim of this study was to assess whether modulated electro-hyperthermia (mEHT) can induce an abscopal effect and thereby enhance the antitumor effects of immunotherapy. We used an intratumoral dendritic cell (DC) injection and mEHT to treat C3H/He mice inoculated with squamous cell carcinoma SCCVII cells in the left leg, and we assessed the whole body antitumor effects. Tumors were examined every two or three days in order to assess growth inhibition. The tumor-draining lymph nodes were removed to enable flow cytometric analysis of CD3(+) and CD8(+) cells, whereas immunohistochemistry was used to assess CD8, S100 and Foxp3 expression in the tumors. Additionally, GP96 expression in the tumors from the different treatment groups was measured. In the control group, the mean tumor volume was larger than that in other groups. These results indicated that the combination therapy of an intratumoral DC injection and mEHT evoked systemic antitumor activity. A larger number of CD3(+) and CD8(+) cells were detected by flow cytometric analysis in the DC plus mEHT treatment group. Tumor tissue immunostaining showed that CD8 and S100 were more strongly expressed in the DC plus mEHT treatment group, although Foxp3 expression was much higher in the control group. The GP96 gene expression level in the mEHT group was significantly different from the expression level in the control group. An abscopal effect may be induced by mEHT, and the effect of immunotherapy with DCs was strongly enhanced by the overexpression of GP96. GP96 is thought to be one of the molecules explaining the abscopal effect. Direct intratumoral administration of DCs and mEHT may be a feasible future treatment strategy.