高强度聚焦超声对手术去势后前列腺癌患者抗肿瘤免疫功能的影响

How high intensity focused ultrasound affect the body anti-tumor immunity of prostate cancer patients after surgical castration

目的探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)对中晚期前列腺癌患者手术去势治疗后机体抗肿瘤免疫功能的影响。方法2007年9月至2008年1月在复旦大学附属中山医院行手术去势治疗的中晚期前列腺癌患者23例随机分为2组,HIFU组为去势手术后行HIFU治疗12例,对照组为单纯去势手术11例。HIFU组平均年龄为(70.92±2.04)岁,初始PSA为(117.75±40.93)ng/mL;对照组平均年龄为(73.27±1.31)岁,初始PSA为(119.44±44.68)ng/mL。所有患者分别于治疗前和治疗后抽取静脉血5 mL,两次抽血时间间隔约6周。检测项目包括CD19+、CD4+CD25+Foxp3+调节性T细胞、VEGF、TGF-β1、IFN-γ和IL-2。HIFU组与对照组治疗前后对照采用Wilcoxon秩和检验(Wilcoxon rank sum test),两组差值对照取对数采用t检验,取P<0.05有统计学差异。结果HIFU组患者HIFU治疗后TGF-β1(P=0.046)显著降低,CD19+治疗前后无变化,IFN-γ和IL-2较治疗前上升,VEGF较治疗前下降,但均无显著差异。对照组患者去势术后CD4+CD25+Foxp3+调节性T细胞显著上升(P=0.020),CD19+、IFN-γ和IL-2较前下降,VEGF和TGF-β1比治疗前上升,但均无显著差异。HIFU组治疗前后差值与对照组治疗前后差值比较,IL-2(P=0.0151)呈显著上升,CD4+CD25+Foxp3+调节性T细胞(P=0.023 0)、VEGF(P=0.001 7)和TGF-β1(P=0.000 6)呈显著降低。结论HIFU治疗可在一定程度上提高去势术后前列腺癌患者的机体抗肿瘤功能,其机制可能通过降低机体免疫抑制和分泌免疫促进因子等实现。

Objective To investigate the effect of high intensity focused ultrasound （HIFU） on the body anti-tumor immunity of intermediate and advanced prostate cancer patients after surgical castration. Methods Twenty-three enrolled cases of intermediate and advanced prostate cancer patients from Sep. 2007 to Jan. 2008 were randomly divided into 2 groups. Twelve were conducted by HIFU after surgical castration and other 11 had sole surgical castration. Among HIFU treated cohorts, the mean age was （70. 92 ±2.04）years old and the mean level of initial PSA was （117.75 ± 40.93）ng/mL. Among the control cohorts, the mean age was （73.27 ± 1.31）years and the mean level of initial PSA was （119.44 ±44.68）ng/mL. No statistical difference was found between the 2 groups. We collected the venous blood before and after all treatments in the invervals of 6 weeks. Test items included CD19^＋ ,CD4^＋ CD25^＋ Foxp3^＋ Treg cell, VEGF, TGF-β1, IFN-yand IL-2. Results In the HIFU-treated patients, TGF-γ cut down significantly after HIFU （P = 0.0463） ; the remaining difference had no statictical significance, IFN-7 and IL-2 rose, VEGF stepped down and CD19^＋ had no difference. In the control cohorts, CD4^＋ CD25^＋ Foxp3^＋ treg cell rose significantly after HIFU （P = 0. 019 7）; while the remaining items were not statistically changed; CD19^＋ , IFN-γ and IL-2 rose, VEGF and TGF-β1 cut down. Comparison between the two groups, the value difference of pre- and post-treatment had statistical meaning. After the treatment of HIFU IL-2 （P = 0. 015 1 ） rose significantly, and CD4^＋ CD25^＋ Foxp3^＋ Treg cell （P = 0. 023 0）, VEGF （P = 0. 001 7） and TGF-β1 （P = 0. 000 6） cut down significantly. Conclusions Intermediate and advanced prostate cancer patients have an immune depression after surgical castration. HIFU can remove this kind of depression in some extent and effectively increase their anti-tumor immunity. Its mechanism maybe is by relieving immune depression and secreting immune facilitating factors.