IL-17 mediated inflammation promotes tumor growth and progression in the skin.
IL-17 mediated inflammation promotes tumor growth and progression in the skin.
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DOI：
10.1371/journal.pone.0032126
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
He D;Li H;Yusuf N;Elmets CA;Athar M;Katiyar SK;Xu H
炎症相关的肿瘤发展机制是肿瘤生物学和免疫学的中心问题，仍有待充分阐明。虽然IL-17与炎症介导的致癌作用有关，但其机制在很大程度上是难以捉摸的。在目前的研究中，我们发现IL-17受体-A基因缺陷（IL-17 R-/-）小鼠对化学致癌剂诱导的皮肤癌发生具有抗性，这是一种建立良好的皮肤炎症相关肿瘤模型。IL-17 R的缺乏增加了CD 8 + T细胞的浸润，而它抑制了CD 11b+骨髓细胞的浸润和髓源性抑制细胞的发育。在IL-17 R-/-小鼠中，炎症诱导的皮肤增生和促肿瘤炎症分子的产生受到抑制。我们发现，皮肤中预先存在的炎症增加了对肿瘤生长的易感性，这与肿瘤特异性IL-17产生T细胞的发展增加有关。这种炎症诱导的对肿瘤生长的易感性在IL-17 R-/-小鼠中被消除。最后，在已经发展出化学致癌物诱导的皮肤肿瘤的小鼠中中和IL-17可以在晚期抑制炎症介导的肿瘤进展。这些结果表明，IL-17介导的炎症是炎症介导的促进肿瘤发展的重要机制。该研究对靶向IL-17预防和治疗肿瘤具有重要意义。
The mechanism for inflammation associated tumor development is a central issue for tumor biology and immunology and remains to be fully elucidated. Although IL-17 is implicated in association with inflammation mediated carcinogenesis, mechanisms are largely elusive. In the current studies, we showed that IL-17 receptor-A gene deficient (IL-17R-/-) mice were resistant to chemical carcinogen-induced cutaneous carcinogenesis, a well-established inflammation associated tumor model in the skin. The deficiency in IL-17R increased the infiltration of CD8+ T cells whereas it inhibited the infiltration of CD11b+ myeloid cells and development of myeloid derived suppressor cells. Inflammation induced skin hyperplasia and production of pro-tumor inflammatory molecules were inhibited in IL-17R-/- mice. We found that pre-existing inflammation in the skin increased the susceptibility to tumor growth, which was associated with increased development of tumor specific IL-17 producing T cells. This inflammation induced susceptibility to tumor growth was abrogated in IL-17R-/- mice. Finally, neutralizing IL-17 in mice that had already developed chemical carcinogen induced skin tumors could inhibit inflammation mediated tumor progression at late stages. These results demonstrate that IL-17 mediated inflammation is an important mechanism for inflammation mediated promotion of tumor development. The study has major implications for targeting IL-17 in prevention and treatment of tumors.
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DOI：
10.4049/jimmunol.0902574
发表时间：
2010-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He D;Li H;Yusuf N;Elmets CA;Li J;Mountz JD;Xu H
通讯作者：
Xu H
影响因子：
15.9
作者：
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通讯作者：
Hagemann, Thorsten
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI
DOI：
10.4049/jimmunol.0804253
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hanson EM;Clements VK;Sinha P;Ilkovitch D;Ostrand-Rosenberg S
通讯作者：
Ostrand-Rosenberg S
影响因子：
30.5
作者：
Hsu, Hui-Chen;Yang, PingAr;Mountz, John D.
通讯作者：
Mountz, John D.