Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis
Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis
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DOI：
10.1073/pnas.0708594105
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发表时间：
2008-01-15
影响因子：
11.1
通讯作者：
Smyth, Mark J.
中科院分区：
文献类型：
--
作者：
Swann, Jeremy B.;Vesely, Matthew D.;Smyth, Mark J.
在这里，我们报道了toll样受体相关信号适配器髓细胞分化因子88 （MyD88）缺失对两种不同的小鼠癌变模型中肿瘤诱导的影响。7,12-二甲基苯[a]蒽(DMBA)/12- o -十四烷酰磷- 13-乙酸（TPA）诱导的皮肤乳头状瘤模型依赖于促炎过程，而3'-甲基蒽（MCA）诱导的纤维肉瘤已被肿瘤免疫学家用于阐明癌症的先天和适应性免疫监测。当暴露于DMBA/TPA组合时，缺乏MyD88的小鼠形成的皮肤乳头瘤比以类似方式处理的基因匹配的WT对照组少。然而，出乎意料的是，当暴露于MCA时，MyD88（-/-）小鼠形成肉瘤的数量少于WT对照组。相比之下，myd88缺陷小鼠在排斥高免疫原性移植肿瘤（包括MCA肉瘤）方面没有表现出缺陷能力。尽管有报道称TNF在慢性炎症中起作用，但TNF缺陷小鼠明显比WT小鼠更容易发生mca诱导的肉瘤。总的来说，这些数据不仅证实了MyD88在促进肿瘤发展中的关键作用，也证明了炎症诱导的致癌和癌症免疫编辑确实可以发生在同一小鼠肿瘤模型中。
Here we report the effects of loss of the Toll-like receptor-associ ated signaling adaptor myeloid-differentiation factor 88 (MyD88) on tumor induction in two distinct mouse models of carcinogenesis. The 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin papilloma model depends on proinflammatory processes, whereas the 3'-methylcholanthrene (MCA) induction of fibrosarcoma has been used by tumor immunologists to illustrate innate and adaptive immune surveillance of cancer. When exposed to a combination of DMBA/TPA, mice lacking MyD88 formed fewer skin papillomas than genetically matched WT controls treated in a similar manner. Unexpectedly, however, fewer MyD88(-/-) mice formed sarcomas than WT controls when exposed to MCA. In contrast, MyD88-deficient mice did not show a defective ability to reject highly immunogenic transplanted tumors, including MCA sarcomas. Despite the reported role of TNF in chronic inflammation, TNF-deficient mice were significantly more susceptible to MCA-induced sarcoma than WT mice. Overall, these data not only confirm the key role that MyD88 plays in promoting tumor development but also demonstrate that inflammation-induced carcinogenesis and cancer immunoediting can indeed occur in the same mouse tumor model.