冷冻消融治疗前列腺癌诱导肿瘤特异性免疫反应

目的:评价经皮冷冻消融治疗局限性前列腺癌前后机体抗肿瘤免疫反应。方法:10例局限性前列腺癌患者行经皮冷冻消融治疗。分别于冷冻治疗前1d、治疗后2周采取外周血,分离外周血单个核细胞(PBMCs)。穿刺活检制备前列腺自身肿瘤和非肿瘤组织溶解物。酶联免疫吸附测定(ELISA)法检测血清TNF-α、IFN-γ、IL-4、IL-10水平,以IFN-γ/IL-4计算Th1/Th2比值。酶联免疫斑点(ELISPOT)试验检测不同组织溶解物刺激下分泌IFN-γ的T细胞数。以人前列腺癌LNCaP细胞和肾癌GRC-1细胞为靶细胞,乳酸脱氢酶(LDH)释放试验检测细胞毒T淋巴细胞(CTL)特异性杀伤活性。结果:与术前比较,冷冻治疗后TNF-α、IFN-γ明显升高,IL-4、IL-10轻度下降,Th1/Th2比值明显升高(P<0.01)。肿瘤组织溶解物刺激后IFN-γ+T细胞数明显增多(P<0.01)。非肿瘤组织溶解物刺激后,IFN-γ+T细胞数无明显变化。冷冻治疗后细胞毒CTL对人前列腺癌细胞株LNCaP特异杀伤活性明显增强,而对人肾癌细胞株GRC-1无明显杀伤活性。随访3～6个月,仅1例患者肿瘤复发。结论:经皮冷冻治疗前列腺癌可诱导机体产生肿瘤特异性免疫反应。

Cryoablation for Prostate Cancer Induces Tumor-Specific Immune Response

Objective： To assess the anti-tumor immune response to percutaneous cryoablation in patients with local prostate cancer. Methods： We treated 10 patients with local prostate cancer by percutaneous cryoablation, collected the blood samples before and 2 weeks after the treatment and isolated peripheral blood mononuclear cells （PBMCs）. Protein lysates were made by biopsy from autologous prostate cancer or non-cancer tissues. The levels of serum TNF-α, IFN-γ, IL-4 and IL-10 were determined by enzyme-linked immunosorbent assay （ELISA） and the Th1/Th2 ratio was calculated by the IFN-γ/IL-4 ratio. The number of IFN-γ^＋ T cells under the stimulation of different protein lysates was counted by enzyme link immunal spot （ELISPOT）. And the cytolytic activity of cytotoxic T lymphocytes （CTL） was detected by LDH assay. Results： Compared with pre-treatment, the levels of TNF-α and IFN-γ the Th1/ Th2 ratio and the number of IFN-γ^＋ T cells induced by tumor protein lysates in PBMCs were increased significantly after cryosurgery （P 〈 0.01 ）, while the levels of IL-4 and IL-10 decreased slightly, and the non-tumor protein lysates induced no obvious changes in the number of IFN-γ^＋ T cells. The cytolytic activity of cytotoxic T lymphocytes against human prostate cancer cells LNCaP was markedly increased, but not that against renal cancer cells GRC-1. One case of recurrence was found during the 3-6 months follow-up. Conclusion： Pereutaneous cryoablation for prostate cancer could induce a tumor-specific immune response.