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目的探讨高强度聚焦超声(high intensity focused ultrasound,HIUF)联合单纯疱疹病毒胸苷激酶/丙氧鸟苷(HSV-tk/GCV)治疗对VX2荷瘤兔的肿瘤免疫耐受和特异性抗肿瘤免疫的影响。方法将40只实验兔按随机数字表法分为对照组、肿瘤组、HIFU组和联合治疗组,每组10只,其中HIFU组给予HIFU单独治疗,联合组给予HIFU和HSV-tk/GCV联合治疗。于治疗后第13天流式细胞术检测各组兔外周血CD4+CD25+Treg(Treg)细胞的数量变化情况,ELISA法检测外周血血浆IL-10,TGF-β的浓度,MTT法检测兔脾淋巴细胞对VX2肿瘤细胞的体外杀伤活性。结果肿瘤组外周血Treg细胞数量[(8.30±0.69)%]、IL-10水平[(67.82±4.52)pg/ml]和TGF-β水平[(6.55±0.45)μg/ml]相对于对照组[(5.30±0.45)%、(54.58±3.53)pg/ml、(5.51±0.27)μg/ml]均显著升高(P<0.01);HIFU组Treg细胞数量[(7.00±0.56)%]、IL-10水平[(60.32±4.70)pg/ml]、TGF-β水平[(6.22±0.19)μg/ml]明显低于肿瘤组(P<0.01,P<0.05);联合治疗组Treg细胞数量[(6.40±0.72)%]和TGF-β水平[(5.86±0.31)μg/ml]低于HIFU组(P<0.05),而IL-10水平[(58.79±4.42)pg/ml]变化则无统计学意义(P>0.05)。杀伤实验显示HIFU组和联合治疗组脾淋巴细胞对VX2肿瘤细胞的杀伤活性分别为(31.62±3.09)%、(29.48±2.68)%,明显高于对照组[(13.94±2.45)%]和肿瘤组[(12.00±2.96)%](P<0.01),但联合治疗组和HIFU组的比较差异无统计学意义(P>0.05)。结论 HIFU联合HSV-tk/GCV治疗后,宿主肿瘤免疫耐受情况得到改善,特异性抗肿瘤免疫力增强。
Objective To investigate the effects of high intensity focused ultrasound (HIUF) combined with herpes simplex virus thymidine kinase / gonadotrophin (HSV-tk / GCV) on tumor immune tolerance and specific anti-tumor immunity in VX2-bearing rabbits Impact. Methods Forty experimental rabbits were randomly divided into control group, tumor group, HIFU group and combination therapy group, with 10 in each group. HIFU group was treated with HIFU alone and combined with HIFU and HSV-tk / GCV treatment. The changes of CD4 + CD25 + Treg (Treg) cells in peripheral blood of each group were detected by flow cytometry on the 13th day after treatment. The levels of IL-10 and TGF-β in peripheral blood were measured by ELISA, In vitro cytotoxic activity of spleen lymphocytes against VX2 tumor cells. Results Compared with the control group, the number of Treg cells in the peripheral blood of the tumor group was significantly higher than that of the control group [(8.30 ± 0.69)%], IL-10 level (67.82 ± 4.52) pg / ml and TGF- (P <0.01). The number of Treg cells in HIFU group was significantly higher than that in HIFU group [(5.30 ± 0.45)% vs (54.58 ± 3.53) pg / ml, The level of IL-10 in the combined group was significantly higher than that in the tumor group [(60.32 ± 4.70) pg / ml] and TGF-β level (6.22 ± 0.19 μg / ml, P <0.01, P < The level of IL-10 was significantly lower than that of HIFU group [(6.40 ± 0.72)%] and TGF-β level [(5.86 ± 0.31) μg / ml] No statistical significance (P> 0.05). The killing experiments showed that the killing activity of spleen lymphocytes to VX2 tumor cells in HIFU group and combination therapy group were (31.62 ± 3.09)% and (29.48 ± 2.68)%, respectively, which were significantly higher than those in control group [(13.94 ± 2.45)%] and tumor Group [(12.00 ± 2.96)%] (P <0.01), but there was no significant difference between the combination therapy group and the HIFU group (P> 0.05). Conclusions After HIFU combined with HSV-tk / GCV treatment, the immune tolerance of the host tumor is improved and the specific anti-tumor immunity is enhanced.