IL-7 Receptor Blockade Inhibits IL-17-Producing γδ Cells and Suppresses Melanoma Development
IL-7 Receptor Blockade Inhibits IL-17-Producing γδ Cells and Suppresses Melanoma Development
复制标题
DOI：
10.1007/s10753-014-9869-2
复制
发表时间：
2014-10-01
期刊：
影响因子：
5.1
通讯作者：
Lu, Hongda
中科院分区：
文献类型：
--
作者：
Li, Jun;Liu, Jian;Lu, Hongda
为了了解肿瘤细胞如何逃避免疫监视机制，从而开发抗肿瘤疗法，研究免疫系统与肿瘤微环境相互作用的机制至关重要。在我们目前的研究中，野生型小鼠接种黑色素瘤细胞系B16-F10（1 × 10（6）/小鼠），并用抗IL-7 R抗体或重组小鼠IL-7（rmIL-7）治疗。与对照组相比，抗IL-7 R抗体处理的小鼠中黑色素瘤细胞系B16-F10的生长被显著抑制，而rmIL-7处理的小鼠中黑色素瘤细胞系B16-F10的生长被显著促进。从抗IL-7 R抗体处理的小鼠中检测到肿瘤组织中髓源性抑制细胞（MDSC）和γ δ细胞的数量减少。接下来，施用抗IL-7 R抗体显著阻断肿瘤中IL-17（+）γ δ细胞的富集。此外，在我们进一步的实验中，用p-Stat 3抑制剂消除了由rmIL-7诱导的促进的黑色素瘤发展。rmIL-7诱导的产生IL-17的γ δ 27（-）细胞的比例和绝对数量的增加也被p-Stat 3抑制剂给药消除，并且通过额外使用Ad-IL-17逆转了抗IL-7 R抗体治疗诱导的抑制的黑色素瘤发展。总之，IL-7/IL-7 R-Stat 3-IL-17通路促进黑素瘤生长，并且IL-7/IL-7 R-Stat 3-IL-17通路的抑制可能有助于黑素瘤小鼠模型中的肿瘤生长。
In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, wild-type mice are inoculated with melanoma cell line B16-F10 (1 x 10(6)/mouse) and treated with anti-IL-7R antibody or recombined mouse IL-7 (rmIL-7). Growth of melanoma cell line B16-F10 was significantly inhibited in anti-IL-7R antibody-treated mice and markedly promoted in rmIL-7-treated mice compared with that in control. A decreased number of myeloid-derived suppressor cells (MDSCs) and gamma delta cells in tumor tissues were detected from anti-IL-7R antibody-treated mice. Next, administration of the anti-IL-7R antibody significantly blocked the enrichment in IL-17(+) gamma delta cells in tumor. Moreover, in our further experiment, promoted melanoma development induced by rmIL-7 was abrogated with p-Stat3 inhibitor. The increased proportion and absolute number of IL-17-producing gamma delta 27(-) cell induced by rmIL-7 were also abolished with the p-Stat3 inhibitor administration, and the suppressed melanoma development induced by anti-IL-7R antibody treatment was reversed with additional use of Ad-IL-17. In conclusion, IL-7/IL-7R-Stat3-IL-17 pathway promotes melanoma growth, and inhibition of IL-7/IL-7R-Stat3-IL-17 pathway may contribute to tumor growth in murine models of melanoma.