TNF Counterbalances the Emergence of M2 Tumor Macrophages.
TNF Counterbalances the Emergence of M2 Tumor Macrophages.
复制标题
DOI：
10.1016/j.celrep.2015.08.033
复制
发表时间：
2015-09-22
期刊：
影响因子：
8.8
通讯作者：
Murray PJ
中科院分区：
文献类型：
--
作者：
Kratochvill F;Neale G;Haverkamp JM;Van de Velde LA;Smith AM;Kawauchi D;McEvoy J;Roussel MF;Dyer MA;Qualls JE;Murray PJ
癌症是一种不消退的持续性炎症，其中不同数量的肿瘤相关巨噬细胞（TAM）浸润并在抗肿瘤M1和促肿瘤M2表型之间采用不同的活化状态。在这里，我们解决了一个级联导致差异巨噬细胞表型在肿瘤微环境。TNF mRNA产生的减少或I型TNF受体信号传导的丧失导致M2 mRNA表达增强的显著模式。M2基因表达部分由来自与炎性单核细胞共募集的嗜酸性粒细胞的IL-13驱动，这是一种受TNF抑制的途径。我们的数据定义了肿瘤微环境中平衡M1和M2群体的调节节点。我们的研究结果表明，癌症中的巨噬细胞极化是动态的，并依赖于TNF和IL-13之间的平衡，从而提供了一种操纵TAM的策略。
Cancer is a form of non-resolving, persistent inflammation where varying numbers of tumor-associated macrophages (TAMs) infiltrate and adopt different activation states between anti-tumor M1 and pro-tumor M2 phenotypes. Here we resolve a cascade causing differential macrophage phenotypes in the tumor microenvironment. Reduction in TNF mRNA production or loss of Type I TNF receptor signaling resulted in a striking pattern of enhanced M2 mRNA expression. M2 gene expression was driven in part by IL-13 from eosinophils co-recruited with inflammatory monocytes, a pathway that was suppressed by TNF. Our data define regulatory nodes within the tumor microenvironment that balance M1 and M2 populations. Our results show macrophage polarization in cancer is dynamic and dependent on the balance between TNF and IL-13, thus providing a strategy for manipulating TAMs.