IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells.
IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells.
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DOI：
10.4049/jimmunol.0902574
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发表时间：
2010-03-01
期刊：
影响因子：
--
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;Li J;Mountz JD;Xu H
免疫应答在肿瘤发展中的作用是肿瘤生物学和免疫学的中心问题。IL-17是炎症和自身免疫性疾病的重要细胞因子。虽然在癌症患者和荷瘤小鼠中检测到产生IL-17的细胞，但IL-17在肿瘤发展中的作用是有争议的，其机制仍有待充分阐明。在目前的研究中，我们发现，在IL-17受体A（IL-17 R）缺陷小鼠中，肿瘤的发展受到抑制。与野生型动物相比，IFN-γ受体缺陷增加肿瘤生长，而IL-17 R和IFN-γR缺陷的小鼠中肿瘤生长受到抑制。进一步的实验表明，通过抗体中和IL-17抑制野生型小鼠中的肿瘤生长，而全身施用IL-17促进肿瘤生长。IL-17 R缺乏增加了CD 8 T细胞浸润，而它减少了肿瘤中髓源性抑制细胞（MDSC）的浸润。相比之下，IL-17的施用抑制了CD 8 T细胞浸润并增加了肿瘤中的MDSC。进一步分析表明，IL-17是荷瘤小鼠MDSC发育和促瘤活性所必需的。这些数据表明，IL-17介导的应答通过在肿瘤部位诱导促肿瘤微环境来促进肿瘤发展。IL-17介导的MDSC调节是其肿瘤促进作用的主要机制。该研究为IL-17在肿瘤发展中的作用提供了新的见解，并对靶向IL-17治疗肿瘤具有重要意义。
The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17 producing cells are detected in cancer patients and tumor bearing mice, the role of IL-17 in tumor development is controversial and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17 receptor A (IL-17R) deficient mice. A defect in IFN-γ receptor increased tumor growth whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-γR compared to wild type animals. Further experiments showed that neutralization of IL-17 by antibodies inhibited tumor growth in wild type mice whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration whereas it reduced the infiltration of myeloid derived suppressor cells (MDSC) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSC in tumors. Further analysis indicated that IL-17 was required for the development and tumor promoting activity of MDSC in tumor bearing mice. These data demonstrate that IL-17 mediated responses promote tumor development through the induction of tumor promoting microenvironments at tumor sites. IL-17 mediated regulation of MDSC is a primary mechanism for its tumor promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.
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影响因子：
100.3
作者：
Dong, C
通讯作者：
Dong, C
影响因子：
4.6
作者：
Honorati, MC;Neri, S;Facchini, A
通讯作者：
Facchini, A
影响因子：
4.4
作者：
Kryczek, Ilona;Wei, Shuang;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
15.9
作者：
Charles, Kellie A.;Kulbe, Hagen;Hagemann, Thorsten
通讯作者：
Hagemann, Thorsten
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