T helper 17 cells promote cytotoxic T cell activation in tumor immunity.
T helper 17 cells promote cytotoxic T cell activation in tumor immunity.
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DOI：
10.1016/j.immuni.2009.09.014
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发表时间：
2009-11-20
期刊：
影响因子：
32.4
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Martin-Orozco N;Muranski P;Chung Y;Yang XO;Yamazaki T;Lu S;Hwu P;Restifo NP;Overwijk WW;Dong C
尽管在人类肿瘤组织中发现了T辅助17(Th17)细胞，但其在肿瘤免疫中的作用尚不清楚。在这里，我们发现IL-17缺乏的小鼠更容易患上肺部黑色素瘤。相反，采用肿瘤特异性Th17细胞的过继T细胞治疗可以防止肿瘤的发展。重要的是，供者Th17细胞保留了其细胞因子的表达表型，并显示出比Th1细胞更强的治疗效果。出乎意料的是，使用Th17而不是Th1细胞的治疗引起了肿瘤特异性CD8+T细胞的显著激活，这是抗肿瘤效果所必需的。Th17细胞促进树突状细胞向肿瘤组织募集，并使引流淋巴结内含有肿瘤物质的CD8CD8α+树突状细胞数量显著增加。此外，与Th1细胞相比，Th17细胞促进了肿瘤组织中CCL20趋化因子的产生，荷瘤CCR6缺陷小鼠对Th17治疗的反应完全受损。我们的数据表明，Th17细胞引发保护性炎症，最终促进肿瘤特异性CD8+T细胞的激活。这些发现对抗肿瘤免疫治疗具有重要意义。
Although T helper 17 (Th17) cells have been found in human tumor tissues, their function in cancer immunity is unclear. Here we show that IL-17-deficient mice were more susceptible to the development of lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the donor Th17 cells retained their cytokine expression phenotype and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 but not Th1 cells elicited a remarkable activation of tumor-specific CD8+ T cells, which were necessary for the anti-tumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and greatly increased the numbers of CD8α+ dendritic cells containing tumor materials in draining lymph nodes. Moreover, compared to Th1 cells, Th17 cells promoted CCL20 chemokine production in tumor tissues and tumor-bearing CCR6-deficient mice were completely impaired in responding to Th17 therapy. Our data indicate that Th17 cells elicit a protective inflammation that ultimately promotes the activation of tumor-specific CD8+ T cells. These findings have important implications in anti-tumor immunotherapies.
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