Recent advances on the immunomodulatory effects of IFN-α: Implications for cancer immunotherapy and autoimmunity
Recent advances on the immunomodulatory effects of IFN-α: Implications for cancer immunotherapy and autoimmunity
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DOI：
10.3109/08916930903510880
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发表时间：
2010-04-01
期刊：
影响因子：
3.5
通讯作者：
Belardelli, Filippo
中科院分区：
文献类型：
--
作者：
Rizza, Paola;Moretti, Franca;Belardelli, Filippo
干扰素α(IFNS-α)是属于I型干扰素家族的多效性细胞因子，最初被描述为具有抗病毒活性。这些细胞因子在某些类型的癌症和病毒性疾病患者中的临床应用记录由来已久。值得注意的是，某些自身免疫性疾病被认为是由内源性干扰素-α介导的，并且经常在一些接受干扰素治疗的患者中观察到。干扰素-α可诱导多种生物学效应，包括诱导/促进细胞凋亡和抑制细胞生长。此外，这些细胞因子还能促进宿主免疫细胞的分化和活性。在小鼠肿瘤模型中的早期研究表明，在注射干扰素或经基因改造产生干扰素-α的肿瘤细胞后，宿主免疫机制在产生持久的抗肿瘤反应中的重要性。多项研究表明，干扰素-α可诱导单核细胞快速分化为高活性的树突状细胞(DC)。值得注意的是，这些DC(干扰素-DC)在吸收复杂抗原和诱导T细胞和B细胞免疫方面特别有效。这些结果综合表明，干扰素-DC在产生抗肿瘤T细胞免疫中发挥作用，指出这些细胞可以成功地用于癌症免疫治疗的策略。同样，干扰素-α-DC的相互作用也可能在一些自身免疫性疾病的发病机制中发挥作用，这些疾病通常与干扰素-α治疗有关。所有这些都揭示了在正常和病理条件下干扰素-α-DC相互作用的复杂性，并刺激了进一步的研究，以确定在患者中使用这些细胞因子或控制其产生/作用的最佳方式。
Interferons alpha (IFNs-alpha) are pleiotropic cytokines belonging to the type I IFN family, originally described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer and viral diseases. Notably, certain autoimmune disorders have been postulated to be mediated by endogenous IFN-alpha and are often observed in some IFN-treated patients. IFN-alpha can induce multiple biological effects, including induction/promotion of apoptosis and inhibition of cell growth. In addition, these cytokines promote the differentiation and activity of host immune cells. Early studies in mouse tumor models showed the importance of host immune mechanisms in the generation of a long-lasting antitumor response after injection of the animals with either IFN or tumor cells genetically modified for IFN-alpha production. Several studies have shown that IFN-alpha can induce the rapid differentiation of monocytes into highly activated dendritic cells (DCs). Of note, these DCs (IFN-DCs) are particularly effective in taking up complex antigens and inducing T- and B-cell immunity. The ensemble of these results suggests that IFN-DCs can play a role in the generation of antitumor T-cell immunity, pointing out that these cells could be successfully used in strategies of cancer immunotherapy. Likewise, IFN-alpha-DC interactions could also play a role in the pathogenesis of some autoimmune disorders, often associated with IFN-alpha treatment. All this reveals the complexity of the IFN-alpha-DC interactions under normal and pathological conditions and stimulates further studies for identifying optimal modalities in either using these cytokines or controlling their production/action in patients.