Ortiz Angélica, Fuchs Serge Y
Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cytokine. 2017 Jan;89:4-11. doi: 10.1016/j.cyto.2016.01.010. Epub 2016 Jan 25.
The anti-tumorigenic effects that type 1 interferons (IFN1) elicited in the in vitro studies prompted consideration of IFN1 as a potent candidate for clinical treatment. Though not all patients responded to IFN1, clinical trials have shown that patients with high risk melanoma, a highly refractory solid malignancy, benefit greatly from intermediate IFN1 treatment in regards to relapse-free and distant-metastasis-free survival. The mechanisms by which IFN1 treatment at early stages of disease suppress tumor recurrence or metastatic incidence are not fully understood. Intracellular IFN1 signaling is known to affect cell differentiation, proliferation, and apoptosis. Moreover, recent studies have revealed specific IFN1-regulated genes that may contribute to IFN1-mediated suppression of cancer progression and metastasis. In concert, expression of these different IFN1 stimulated genes may impede numerous mechanisms that mediate metastatic process. Though, IFN1 treatment is still utilized as part of standard care for metastatic melanoma (alone or in combination with other therapies), cancers find the ways to develop insensitivity to IFN1 treatment allowing for unconstrained disease progression. To determine how and when IFN1 treatment would be most efficacious during disease progression, we must understand how IFN1 signaling affects different metastasis steps. Here, we specifically focus on the anti-metastatic role of endogenous IFN1 and parameters that may help to use pharmaceutical IFN1 in the adjuvant treatment to prevent cancer recurrence and metastatic disease.
1型干扰素（IFN1）在体外研究中产生的抗肿瘤作用促使人们将IFN1视为临床治疗的有力候选药物。尽管并非所有患者都对IFN1有反应，但临床试验表明，高危黑色素瘤患者（一种高度难治的实体恶性肿瘤）在无复发生存和无远处转移生存方面，从接受中等剂量IFN1治疗中获益匪浅。疾病早期阶段进行IFN1治疗抑制肿瘤复发或转移发生率的机制尚未完全明确。已知细胞内IFN1信号传导会影响细胞分化、增殖和凋亡。此外，最近的研究揭示了特定的IFN1调控基因，这些基因可能有助于IFN1介导的癌症进展和转移抑制。这些不同的IFN1刺激基因的表达可能共同阻碍众多介导转移过程的机制。尽管如此，IFN1治疗仍被用作转移性黑色素瘤标准治疗的一部分（单独使用或与其他疗法联合使用），但癌症会产生对IFN1治疗的不敏感性，从而导致疾病不受控制地进展。为了确定在疾病进展过程中IFN1治疗如何以及何时最为有效，我们必须了解IFN1信号传导如何影响不同的转移步骤。在此，我们特别关注内源性IFN1的抗转移作用以及可能有助于在辅助治疗中使用药物性IFN1预防癌症复发和转移性疾病的参数。
