调制式电高热疗法通过远隔效应增强小鼠的树突状细胞疗法。
Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice.
作者信息
Qin Wei, Akutsu Yasunori, Andocs Gabor, Suganami Akiko, Hu Xin, Yusup Gulbostan, Komatsu-Akimoto Aki, Hoshino Isamu, Hanari Naoyuki, Mori Mikito, Isozaki Yuka, Akanuma Naoki, Tamura Yutaka, Matsubara Hisahiro
机构信息
Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of Veterinary Clinical Medicine, Faculty of Veterinary Science, Tottori University, Tottoti 680-8553, Japan.
出版信息
Oncol Rep. 2014 Dec;32(6):2373-9. doi: 10.3892/or.2014.3500. Epub 2014 Sep 19.
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.
本研究的目的是评估调制式电超高温疗法(mEHT)是否能诱导远隔效应,从而增强免疫疗法的抗肿瘤效果。我们采用瘤内注射树突状细胞(DC)和mEHT治疗左下肢接种了鳞状细胞癌SCCVII细胞的C3H/He小鼠,并评估全身抗肿瘤效果。每两到三天检查一次肿瘤以评估生长抑制情况。切除肿瘤引流淋巴结以便对CD3+和CD8+细胞进行流式细胞术分析,而免疫组化用于评估肿瘤中CD8、S100和Foxp3的表达。此外,还测量了不同治疗组肿瘤中GP96的表达。在对照组中,平均肿瘤体积大于其他组。这些结果表明,瘤内注射DC和mEHT的联合疗法引发了全身抗肿瘤活性。在DC加mEHT治疗组中,通过流式细胞术分析检测到更多的CD3+和CD8+细胞。肿瘤组织免疫染色显示,DC加mEHT治疗组中CD8和S100的表达更强,尽管对照组中Foxp3的表达要高得多。mEHT组中GP96基因表达水平与对照组的表达水平有显著差异。mEHT可能诱导远隔效应,并且DC免疫疗法的效果因GP96的过表达而得到显著增强。GP96被认为是解释远隔效应的分子之一。直接瘤内注射DC和mEHT可能是未来一种可行的治疗策略。