Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response.
Sensitivity of human pleural mesothelioma to oncolytic measles virus depends on defects of the type I interferon response.
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DOI：
10.18632/oncotarget.6285
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发表时间：
2015-12-29
期刊：
影响因子：
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通讯作者：
Fonteneau JF
中科院分区：
文献类型：
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作者：
Achard C;Boisgerault N;Delaunay T;Roulois D;Nedellec S;Royer PJ;Pain M;Combredet C;Mesel-Lemoine M;Cellerin L;Magnan A;Tangy F;Grégoire M;Fonteneau JF
减毒麻疹病毒（MV）目前正在临床试验中作为溶瘤病毒进行评估，并可能代表恶性胸膜间皮瘤（MPM）的新治疗方法。在此，我们筛选了22个人MPM细胞系和一些健康的原代细胞对MV感染和复制的敏感性。我们发现，MV复制在15的22个MPM细胞系。尽管与健康细胞相比，大多数MPM细胞系CD46过表达，但我们发现对MV复制的敏感性与这种过表达无关。然后，我们评估了MPM细胞系和健康细胞的抗病毒I型干扰素（IFN）反应。我们发现，健康的细胞和7个不敏感的MPM细胞系开发了一个I型干扰素的反应，在病毒的存在下，从而抑制复制。相比之下，15个敏感的MPM细胞系中的11个在MV存在下不能产生完整的I型IFN应答。最后，我们表明，除了I型干扰素到MV敏感的肿瘤细胞系抑制复制。这些结果表明，在I型IFN反应的缺陷是常见的MPM和MV利用这些缺陷发挥溶瘤活性。
Attenuated measles virus (MV) is currently being evaluated as an oncolytic virus in clinical trials and could represent a new therapeutic approach for malignant pleural mesothelioma (MPM). Herein, we screened the sensitivity to MV infection and replication of twenty-two human MPM cell lines and some healthy primary cells. We show that MV replicates in fifteen of the twenty-two MPM cell lines. Despite overexpression of CD46 by a majority of MPM cell lines compared to healthy cells, we found that the sensitivity to MV replication did not correlate with this overexpression. We then evaluated the antiviral type I interferon (IFN) responses of MPM cell lines and healthy cells. We found that healthy cells and the seven insensitive MPM cell lines developed a type I IFN response in presence of the virus, thereby inhibiting replication. In contrast, eleven of the fifteen sensitive MPM cell lines were unable to develop a complete type I IFN response in presence of MV. Finally, we show that addition of type I IFN onto MV sensitive tumor cell lines inhibits replication. These results demonstrate that defects in type I IFN response are frequent in MPM and that MV takes advantage of these defects to exert oncolytic activity.