Tsavaris N, Kosmas C, Vadiaka M, Kanelopoulos P, Boulamatsis D
Department of Pathophysiology-Oncology Unit, Laikon General Hospital, Athens University School of Medicine, 11527 Athens, Greece.
Br J Cancer. 2002 Jul 1;87(1):21-7. doi: 10.1038/sj.bjc.6600347.
Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1beta, IFN-gamma, GM-CSF, IL-6, TNF-alpha, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by (3)H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-gamma levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-alpha and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-gamma levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P<0.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-gamma, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-alpha levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-gamma, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-alpha. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel.
除细胞毒性外，紫杉烷类还可诱导其他生物学效应，尤其是在免疫系统方面。紫杉烷类已显示出对肿瘤的免疫刺激作用，支持了这些药物通过多种机制而非仅通过抑制细胞分裂来抑制癌症的观点。本研究的目的是评估紫杉烷类（紫杉醇和多西他赛）的作用，并研究它们改变乳腺癌患者重要免疫参数的能力。30例接受化疗的晚期乳腺癌女性被随机分为两组，分别接受单药紫杉醇或多西他赛治疗。通过ELISA检测患者在第一个治疗周期前和最后一个治疗周期后以及正常供体血清中的IL-2、IL-1β、IFN-γ、GM-CSF、IL-6、TNF-α和PGE2水平。在这些相同的血样中，分别在总PBMC群体中检测NK和LAK细胞对NK敏感的K562肿瘤靶标的活性，并通过3H-胸腺嘧啶增殖试验检测自体混合淋巴细胞反应。两组所有患者均对治疗有反应。在健康献血者对照组与两个紫杉烷类治疗组的治疗前值之间，在以下免疫参数方面观察到显著差异；与对照组相比，乳腺癌患者治疗前IL-2、GM-CSF、IFN-γ水平以及NK和LAK细胞细胞毒性降低，而TNF-α和IL-6水平升高。在研究的任何参数方面，两个治疗组之间均无显著差异。两种药物均导致MLR值、NK和LAK细胞细胞毒性以及IL-6、GM-CSF、IFN-γ水平升高，而IL-1、TNF和PGE2水平降低。与紫杉醇相比，多西他赛在这些差异的百分比方面更大（P<0.0001）。更具体地说，与紫杉醇相比，多西他赛在增强MLR、NK、LAK活性以及IFN-γ、IL-2、IL-6和GM-CSF水平方面表现出更明显的效果，并且在降低IL-1和TNF-α水平方面更有效。本研究表明，晚期乳腺癌患者接受单药紫杉醇或多西他赛治疗后，血清IFN-γ、IL-2、IL-6、GM-CSF细胞因子水平升高，PBMC的NK和LAK细胞活性增强，同时两者均导致急性期血清IL-1和TNF-α细胞因子水平降低。此外，在上述所有参数方面，多西他赛的效果比紫杉醇更明显。
