Are we ready to start studies of Th17 cell manipulation as a therapy for cancer?
Are we ready to start studies of Th17 cell manipulation as a therapy for cancer?
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DOI：
10.1007/s00262-011-1151-y
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发表时间：
2012-01-01
影响因子：
5.8
通讯作者：
Pandha, Hardev S.
中科院分区：
文献类型：
--
作者：
Middleton, Gary W.;Annels, Nicola E.;Pandha, Hardev S.
从治疗的角度来看，关于Th 17细胞的新兴文献应该使我们能够决定是否理性地追求在癌症中操纵Th 17细胞。本综述的目的是试图综合一些相互矛盾的结论，这些细胞在肿瘤发生过程中发挥的作用，以提供指导，我们目前的理解是否足以安全地追求Th 17靶向治疗癌症在这个时候。Th 17细胞是一个高度可塑性的群体，Th 17细胞生成和偏斜的细胞因子驱动因素在各种癌症之间会有所不同，重要的是在任何个体患者的不同肿瘤累及部位之间会有所不同。不仅由Th 17细胞而且由其它细胞特别是巨噬细胞产生的促血管生成IL-17的净影响以及Th 1/Th 17细胞的抗肿瘤作用反过来将由多种趋化因子和细胞因子在任何肿瘤微环境中的复杂相互作用决定。不能归巢到肿瘤的Th 17细胞可能是免疫抑制性的。IL-17和Th 17动力学的复杂性使得容易预测增强或抑制Th 17细胞分化在癌症中的作用成问题。
From a therapeutic perspective, the bourgeoning literature on Th17 cells should allow us to decide whether to rationally pursue the manipulation of Th17 cells in cancer. The purpose of this review is to attempt a synthesis of a number of contradictory conclusions as to the role that these cells are playing in the process of tumourigenesis in order to provide guidance as to whether our current understanding is sufficient to safely pursue Th17-targeted therapy in cancer at this time. Th17 cells are a highly plastic population and the cytokine drivers for Th17 cell generation and skewing will vary between various cancers and importantly between different sites of tumour involvement in any individual patient. The net impact of the pro-angiogenic IL-17 produced not only by Th17 cells but by other cells particularly macrophages and the antitumour effects of Th1/Th17 cells will in turn be determined by the complex interplay of diverse chemokines and cytokines in any tumour microenvironment. Th17 cells that fail to home to tumours may be immunosuppressive. The complexity of IL-17 and Th17 dynamics makes easy prediction of the effects of either enhancing or suppressing Th17 cell differentiation in cancer problematic.