IL-2-mediated augmentation of NK-cell activity and activation antigen expression on NK- and T-cell subsets in patients with metastatic melanoma treated with interferon-α and DTIC

IL-2-mediated augmentation of NK-cell activity and activation antigen expression on NK- and T-cell subsets in patients with metastatic melanoma treated with interferon-α and DTIC
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在接受干扰素-α 和 DTIC 治疗的转移性黑色素瘤患者中,IL-2 介导的 NK 细胞活性增强以及 NK 和 T 细胞亚群上的激活抗原表达增强

DOI:
10.1023/a:1027387930868
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发表时间:
2004
影响因子:
4
通讯作者:
I. Spuẑić
I. Spuẑić
中科院分区:
医学3区
文献类型:
--
作者:
G. Konjević;V. Jović;V. Jurišić;S. Radulović;S. Jelić;I. Spuẑić

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考虑到明确和全面的免疫学监测是评价所获得的免疫调节作用的基础,我们评价了NK细胞活性、CD 3 + CD 4+、CD 3 + CD 8 + T细胞和CD 16 + CD 56 + NK细胞的数量,以及CD 56 + NK细胞、CD 8+和CD 3 + T细胞上活化抗原CD 69、CD 38和HLA-DR的表达,在用达卡巴嗪(DTIC)和干扰素-α(IFN-α)进行化学免疫治疗的39例转移性黑色素瘤患者中,同时产生IL-2和TNF-α。在治疗的第一个周期中,NK细胞活性、CD 4 + T辅助细胞数量、CD 4/CD 8 T细胞比率以及NK和T细胞上活化抗原CD 69和CD 38的表达分别显著升高。然而,在随后的周期中,仅活化抗原显著增加,而NK细胞的百分比或活性没有增加。DTIC和IFN-α联合治疗仅在第一个周期出现早期但短暂的免疫增强作用,这表明,尽管IL-2水平升高,与NK细胞活性增强相关,但该治疗的效果有限,可能是由于转移性疾病中持续高水平的TNF-α的不良作用。
Considering that well-defined and comprehensive immunological monitoring is the basis for the evaluation of the obtained immunmodulatory effects, we evaluated NK-cell activity, the number of CD3+CD4+, CD3+CD8+ T cells and CD16+CD56+ NK cells, as well as the expression of activation antigens, CD69, CD38 and HLA-DR on CD56+ NK cells, CD8+ and CD3+ T cells, simultaneously with IL-2 and TNF-α production, during chemoimmunotherapy with dacarbazine (DTIC) and interferon-α (IFN-α) in 39 patients with metastatic melanoma. In the first cycle of therapy, there was a significant rise in NK-cell activity, CD4+ T helper cell number, CD4/CD8 T-cell ratio, and the expression of activation antigens CD69 and CD38, on NK and T cells, respectively. However, in the following cycles there was a significant increase only in activation antigens without an increase in the percent or activity of NK cells. The early, but transient, immunopotentiation, present only in the first cycle of combined DTIC and IFN-α therapy, suggests that, in spite of increased IL-2 level, associated with augmented NK-cell activity, this therapy has a limited effect probably owing to the adverse effect of persistently high level of TNF-α in metastatic disease.
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