Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments
Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments
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DOI：
10.1182/blood-2009-03-208249
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发表时间：
2009-08-06
期刊：
影响因子：
20.3
通讯作者：
Zou, Weiping
中科院分区：
文献类型：
--
作者：
Kryczek, Ilona;Banerjee, Mousumi;Zou, Weiping
Th 17细胞在自身免疫性疾病中发挥积极作用。然而，Th 17细胞在癌症患者中的性质知之甚少。我们研究了201例卵巢癌患者的Th 17细胞，相关机制和临床意义。肿瘤浸润性Th 17细胞表现出多功能效应T细胞表型，与效应细胞正相关，与肿瘤浸润性调节性T细胞负相关。肿瘤相关巨噬细胞通过白细胞介素-1 β（IL-1 β）促进Th 17细胞，而肿瘤浸润调节性T细胞通过腺苷能途径抑制Th 17细胞。此外，通过IL-17和干扰素-γ之间的协同作用，Th 17细胞刺激CXCL 9和CXCL 10的产生以将效应T细胞募集到肿瘤微环境中。CXCL 9和CXCL 10的水平与肿瘤浸润效应T细胞相关。肿瘤浸润性Th 17细胞的水平和腹水IL-17的水平在更晚期的疾病中降低，并积极预测患者的预后。总之，Th 17细胞可能通过诱导Th 1型趋化因子和将效应细胞募集到肿瘤微环境中来促进保护性人类肿瘤免疫。Th 17细胞的抑制代表了一种新的免疫逃避机制。因此，这项研究为开发基于促进癌症患者Th 17细胞群的新型免疫增强策略提供了科学和临床依据。（血。2009; 114：1141-1149）
Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1 beta (IL-1 beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients. (Blood. 2009; 114: 1141-1149)