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[冷冻消融诱导前列腺癌抗肿瘤免疫反应的实验研究]

[Experimental study of anti-tumor immunologic response induced by cryoablation for prostate cancer].

作者信息

Guo Xiu-ying, Si Tong-guo, Guo Zhi, Wang Hai-tao

机构信息

Department of Interventional Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 Apr 13;90(14):952-5.

PMID:20646642
Abstract

OBJECTIVE

To assess the anti-tumor immune response of cryoablation for prostate cancer.

METHODS

Mouse model of prostate cancer was established. And the tumor-bearing mice were divided into three groups: control group (Group A), surgery group (Group B) and cryoablation group (Group C). Blood samples were withdrawn before and at Days 7, 14, 21 post-treatment. IFN-gamma and IL-4 were analyzed by enzyme-linked immunosorbent assay (ELISA). Th1/Th2 ratio was estimated from the IFN-gamma/IL-4 ratio. Lymphocytes of draining lymph node (DLN) and spleen were isolated. And the post-therapeutical number of tumor-specific IFN-gamma+CD4+ Th cells was measured by the method of enzyme link immunological spot (ELISPOT). And tumor-specific cytolytic activity of CD8+ cytotoxic T lymphocyte (CTL) was measured by LDH assay. The rate of metastasis was assessed.

RESULTS

At Day 7 post-treatment in Groups A, B and C, Th1/Th2 ratio was 4.97+/-0.31, 10.07+/-0.62 and 13.71+/-0.57 respectively (P<0.05); the number of IFN-gamma+ cells every 10(6) CD4+ Th cells in DLN 22.3+/-1.0, 24.0+/-1.2 and 243.4+/-46.2 respectively; cytolytic activity of cytotoxic T lymphocyte against prostate cancer cells (14.6+/-1.1)%, (15.2+/-0.8)% and (62.6+/-2.3)% respectively (P<0.05). But for T cells derived from spleen, there were no difference in IFN-gamma+CD4+ Th cells or cytolytic activity of CTL among the groups. At Day 28 post-treatment, the rate of DLN metastasis was 100%, 80% and 40% respectively. And the rates of lung metastasis were all 100%.

CONCLUSION

Cryoablation for prostate cancer can induce the Th1 advantage of anti-tumor immunity and generate the tumor-specific immune response in DLN. But the response remains limited. Further studies are warranted.

摘要

目的

评估前列腺癌冷冻消融的抗肿瘤免疫反应。

方法

建立前列腺癌小鼠模型。将荷瘤小鼠分为三组:对照组(A组)、手术组(B组)和冷冻消融组(C组)。在治疗前及治疗后第7、14、21天采集血样。采用酶联免疫吸附测定(ELISA)法分析干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)。根据IFN-γ/IL-4比值估算Th1/Th2比值。分离引流淋巴结(DLN)和脾脏的淋巴细胞。采用酶联免疫斑点法(ELISPOT)检测治疗后肿瘤特异性IFN-γ+CD4+ Th细胞数量。采用乳酸脱氢酶(LDH)测定法检测CD8+细胞毒性T淋巴细胞(CTL)的肿瘤特异性细胞溶解活性。评估转移率。

结果

治疗后第7天,A、B、C组的Th1/Th2比值分别为4.97±0.31、10.07±0.62和13.71±0.57(P<0.05);每10(6)个DLN中CD4+ Th细胞中IFN-γ+细胞数量分别为22.3±1.0、24.0±1.2和243.4±46.2;细胞毒性T淋巴细胞对前列腺癌细胞的细胞溶解活性分别为(14.6±1.1)%、(15.2±0.8)%和(62.6±2.3)%(P<0.05)。但对于来源于脾脏的T细胞,各组间IFN-γ+CD4+ Th细胞或CTL的细胞溶解活性无差异。治疗后第28天,DLN转移率分别为100%、80%和40%。肺转移率均为100%。

结论

前列腺癌冷冻消融可诱导抗肿瘤免疫的Th1优势,并在DLN中产生肿瘤特异性免疫反应。但该反应仍然有限。有必要进一步研究。

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