Martin-Orozco Natalia, Muranski Pawel, Chung Yeonseok, Yang Xuexian O, Yamazaki Tomohide, Lu Sijie, Hwu Patrick, Restifo Nicholas P, Overwijk Willem W, Dong Chen
Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Immunity. 2009 Nov 20;31(5):787-98. doi: 10.1016/j.immuni.2009.09.014. Epub 2009 Oct 29.
Although T helper 17 (Th17) cells have been found in tumor tissues, their function in cancer immunity is unclear. We found that interleukin-17A (IL-17A)-deficient mice were more susceptible to developing lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the Th17 cells retained their cytokine signature and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 cells elicited a remarkable activation of tumor-specific CD8(+) T cells, which were necessary for the antitumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and in draining lymph nodes increased CD8 alpha(+) dendritic cells containing tumor material. Moreover, Th17 cells promoted CCL20 chemokine production by tumor tissues, and tumor-bearing CCR6-deficient mice did not respond to Th17 cell therapy. Thus, Th17 cells elicited a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. These findings have important implications in antitumor immunotherapies.
尽管在肿瘤组织中发现了辅助性T细胞17（Th17细胞），但其在癌症免疫中的功能尚不清楚。我们发现白细胞介素-17A（IL-17A）缺陷小鼠更易发生肺黑色素瘤。相反，用肿瘤特异性Th17细胞进行过继性T细胞治疗可预防肿瘤发展。重要的是，Th17细胞保留了其细胞因子特征，并且比Th1细胞表现出更强的治疗效果。出乎意料的是，使用Th17细胞进行治疗引发了肿瘤特异性CD8(+) T细胞的显著活化，这对于抗肿瘤作用是必需的。Th17细胞促进树突状细胞募集到肿瘤组织中，并且在引流淋巴结中增加了含有肿瘤物质的CD8α(+) 树突状细胞。此外，Th17细胞促进肿瘤组织产生CCL20趋化因子，并且荷瘤CCR6缺陷小鼠对Th17细胞治疗无反应。因此，Th17细胞引发了一种促进肿瘤特异性CD8(+) T细胞活化的保护性炎症。这些发现对抗肿瘤免疫疗法具有重要意义。
