Lauerova L, Dusek L, Simickova M, Kocák I, Vagundová M, Zaloudík J, Kovarík J
Department of Experimental Oncology, Masaryk Memorial Cancer Institute, Brno, 656 53 Czech Republic.
Neoplasma. 2002;49(3):159-66.
The immunological dysfunction associated with human cancer is well known phenomenon. It comprises number of pathological changes within immune network including imbalance in cytokines of Th1/Th2 origin. The objectives of our study were (i) to evaluate the abnormalities in serum levels of selected cytokines in malignant melanoma patients with regional lymph node metastases as compared to normal values, (ii) to examine the relationship between postoperative cytokine levels and disease progression and (iii) to correlate cytokine profile changes during IFN-alpha therapy with the disease progression and potential therapeutical response. Nine Th1/Th2 related cytokines and sIL-2R were determined in 26 malignant melanoma patients at clinical stage III prior and during adjuvant immunotherapy. Control group consisted of 26 healthy persons. Patients were treated with rIFN-alpha according to EORTC Melanoma group protocol 18952. Cytokines were quantified in patients sera using commercial ELISA kits. Majority of melanoma patients showed significantly lower values of IL-2 and IFN-gamma and pathologically elevated levels of IL-4, IL-6, IL-10 as compared to healthy subjects what indicates disease associated Th1/Th2 imbalance. In addition increased IL-12 and IL-15 values were noted in some patients (54% and 27%, respectively). All patients who manifested early relapse during immunotherapy had significantly lower pretreatment levels of IL-2 and IL-12 than those remaining without progression and probably benefiting from the treatment. Cytokine changes during immunotherapy disclosed that decreases in IL-2 and IL-12 and raises in IL-6 and IL-10 values occurred at least one month prior to relapse. Moreover, the continuous elevation of TNF-alpha and sIL-2R could be observed in patients who remained without progression during 10 months lasting immunotherapy. Our data illustrate that malignant melanoma associates with Th1/Th2 perturbances which are directed towards extended Th2 responses and that measurement of selected cytokines of Th1/Th2 category may be used as an early signal of disease deterioration and for evaluation of immunotherapy response.
与人类癌症相关的免疫功能障碍是一种众所周知的现象。它包括免疫网络内的一些病理变化，包括Th1/Th2来源的细胞因子失衡。我们研究的目的是：（i）评估伴有区域淋巴结转移的恶性黑色素瘤患者血清中所选细胞因子水平与正常值相比的异常情况；（ii）检查术后细胞因子水平与疾病进展之间的关系；（iii）将干扰素-α治疗期间细胞因子谱的变化与疾病进展和潜在治疗反应相关联。在26例临床III期恶性黑色素瘤患者辅助免疫治疗前及治疗期间，测定了9种Th1/Th2相关细胞因子和sIL-2R。对照组由26名健康人组成。患者按照欧洲癌症研究与治疗组织（EORTC）黑色素瘤组方案18952接受重组干扰素-α治疗。使用商用ELISA试剂盒对患者血清中的细胞因子进行定量。与健康受试者相比，大多数黑色素瘤患者的IL-2和干扰素-γ值显著降低，而IL-4、IL-6、IL-10水平病理性升高，这表明疾病相关的Th1/Th2失衡。此外，一些患者（分别为54%和27%）的IL-12和IL-15值也有所升高。所有在免疫治疗期间早期复发的患者，其治疗前IL-2和IL-12水平明显低于未进展且可能从治疗中获益的患者。免疫治疗期间的细胞因子变化表明，IL-2和IL-12的降低以及IL-6和IL-10值的升高至少在复发前一个月就已出现。此外，在持续10个月的免疫治疗期间未进展的患者中，可以观察到TNF-α和sIL-2R持续升高。我们的数据表明，恶性黑色素瘤与Th1/Th2紊乱相关，这种紊乱导致Th2反应增强，并且测定Th1/Th2类别的所选细胞因子可作为疾病恶化的早期信号以及评估免疫治疗反应的指标。
