University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.
Ann N Y Acad Sci. 2009 Dec;1182:47-57. doi: 10.1111/j.1749-6632.2009.05073.x.
Interferon alpha2b (IFN-alpha2b) at high dosage is critical to the reversal of signaling defects in T cells of melanoma patients, and to the durable effector (alpha DC1) polarization of dendritic cells. These immunoregulatory effects appear to be uniquely achieved with levels of IFN-alpha only attainable in vivo using the high-dose regimen of IFN-alpha2b (HDI). Three US cooperative group studies have evaluated the benefit of HDI as an adjuvant therapy for high-risk melanoma. All have demonstrated significant and durable reduction in the frequency of relapse, while the first and third trials have demonstrated significant improvements in the fractions of patients surviving compared with observation (E1684) or with a ganglioside vaccine (GMK, E1694). A meta-analysis of 13 randomized trials evaluating adjuvant IFN therapy has now also demonstrated significant benefits for IFN in terms of RFS and OS. Research of IFN-alpha in melanoma is now focused on identifying prognostic markers of outcome and predictors of therapeutic response.
高剂量干扰素 alpha2b（IFN-alpha2b）对于逆转黑色素瘤患者 T 细胞信号缺陷以及树突状细胞的持久效应（alpha DC1）极化至关重要。这些免疫调节作用似乎是通过体内使用高剂量 IFN-alpha2b（HDI）方案才能达到的 IFN-alpha 水平独特地实现的。三个美国合作组研究评估了 HDI 作为高危黑色素瘤辅助治疗的益处。所有研究均表明复发频率显著且持久降低，而第一和第三次试验表明与观察（E1684）或神经节苷脂疫苗（GMK，E1694）相比，存活患者的比例显著提高。对 13 项随机试验评估辅助 IFN 治疗的荟萃分析也表明 IFN 在 RFS 和 OS 方面具有显著益处。目前，对黑色素瘤中 IFN-alpha 的研究重点是确定预后标志物和治疗反应的预测因子。
