氩氦刀治疗晚期非小细胞肺癌免疫增强作用的研究

The immune-enhancing effect of Ar-He targeted cryoablation for the treatment of advanced non-small cell lung cancer

目的:探讨氩氦刀冷冻治疗晚期非小细胞肺癌的免疫调节作用。方法:选择100例晚期非小细胞肺癌患者,应用ELISA法测定氩氦刀治疗前和治疗后10 d血清IL-2,TNFα-,IL-12浓度。同时提取外周血单个核细胞作为效应细胞,以人肺癌细胞株SPC-A-1和人红白血病细胞株K562作为靶细胞,用MTT法测定NK细胞和细胞毒性T细胞(CTL)的活性以及T细胞亚群。结果:氩氦刀治疗后病灶消失3例,病灶缩小50%以上者为34例,病灶稳定47例,病灶进展16例,1年生存率43%,中位治疗到疾病进展时间(TTP)4个月。对肿瘤细胞非特异性杀伤(NK)能力和特异性杀伤(CTL)能力提高,分别增加83%和67%。血清中IL-2,TNFα-,IL-12水平明显增高。非小细胞肺癌患者CD3+,CD4+,CD4+/CD8+T细胞表达均有所提高。结论:氩氦刀局部治疗非小细胞肺癌患者不仅可以从影像学上观察到治疗效果,而且可以调动和激发患者自身的免疫功能,尤其对年老体弱,不能耐受手术治疗者,氩氦刀局部治疗提供了有效的治疗手段。

Objective,To investigate immune-regulating effects of Ar-He targeted cryoablation for the treatment of the advanced non small cell lung cancer （NSCLC）. Methods. One hundred NSCLC patients were enrolled in this study. The serum levels of IL-2, TNF-α and IL-12 were measured by enzyme-linked immunosorbent assay （ELISA） before and 10 days after Ar-He targeted cryoablation. Low-density mononuclear cells （MNC） were separated by Ficoll-Hypaque as effector cells. Human lung cancer SPC-A1 and K562 cells were selected as target cells. The activities of natural killer （NK） cells and cytotoxic T-lymphocytes （CTL） were determined by MTT assay. Results;Of the 100 patients, 3 cases achieved complete remission （CR）, 34 cases achieved 〉 50% remission （PR）, 47 cases had stable disease （SD）, and 16 cases had progressive disease （PD）. The one-year survival rate was 43% and the median survival time to progression was 4 months. The non specific tumor-killing ability of NK cells increased by 83% and the specific tumor-kill- ing activity of CTL increased by 67%. The serum levels of IL-2, TNF-α, and IL-12 were elevated significantly. The positive expression of CD3 ^＋ and CD4 ^＋on T cells and the ratio of CD4^＋/CD8^＋also increased. Conclusion：The effectiveness of Ar-He targeted cryoablation for the local treatment of NSCLC could be observed by imaging analysis. Ar-He targeted cryoablation regulates and stimulates self immunological function of NSCLC patients. Ar-He targeted cryoablation provides an effective method especially for old and surgery nontolerant patients.