Department of Respiratory Diseases, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Immunol. 2010 Nov 15;185(10):6348-54. doi: 10.4049/jimmunol.1001728. Epub 2010 Oct 15.
IL-17-producing CD4(+) T (Th17) cells have been found to be increased in some human cancers; however, the possible implication of Th17 cells in regulating antitumor responses in malignant pleural effusion (MPE) remains to be elucidated. In the current study, distribution and phenotypic features of Th17 cells in both MPE and peripheral blood from patients with lung cancer were determined by flow cytometry or double immunofluorescence staining. The impacts of cytokines on Th17 cell generation and differentiation were explored. The chemoattractant activity of chemokines CCL20 and CCL22 for Th17 cells in vitro was also observed. It was found that the increased Th17 cells could be found in MPE compared with blood. The in vitro experiments showed that IL-1β, IL-6, IL-23, or their various combinations could promote Th17 cell generation and differentiation from naive CD4(+) T cells. MPE was chemotactic for Th17 cells, and this activity was partly blocked by anti-CCL20 and/or CCL22 Abs. Our data also showed that the accumulation of Th17 cells in MPE predicted improved patient survival. It could be concluded that the overrepresentation of Th17 cells in MPE might be due to Th17 cell differentiation and expansion stimulated by pleural proinflammatory cytokines and to recruitment of Th17 cells from peripheral blood induced by pleural chemokines CCL20 and CCL22. Furthermore, the accumulation of Th17 cells in MPE predicted improved patient survival. These data provide the basis for developing immune-boosting strategies based on ridding the cancer patient of this cell population.
白细胞介素-17 产生的 CD4(+)T（Th17）细胞在一些人类癌症中被发现增加；然而，Th17 细胞在调节恶性胸腔积液（MPE）中的抗肿瘤反应的可能影响仍有待阐明。在本研究中，通过流式细胞术或双免疫荧光染色确定了肺癌患者的 MPE 和外周血中 Th17 细胞的分布和表型特征。还探讨了细胞因子对 Th17 细胞生成和分化的影响。还观察了趋化因子 CCL20 和 CCL22 对 Th17 细胞在体外的趋化活性。结果发现，与血液相比，MPE 中可发现增加的 Th17 细胞。体外实验表明，IL-1β、IL-6、IL-23 或其各种组合可促进幼稚 CD4(+)T 细胞生成和分化为 Th17 细胞。MPE 对 Th17 细胞具有趋化性，这种活性可被抗 CCL20 和/或 CCL22 Abs 部分阻断。我们的数据还表明，Th17 细胞在 MPE 中的积累预测患者生存率提高。可以得出结论，MPE 中 Th17 细胞的过度表达可能是由于胸膜前炎症细胞因子刺激 Th17 细胞分化和扩增，以及由胸膜趋化因子 CCL20 和 CCL22 从外周血募集 Th17 细胞所致。此外，Th17 细胞在 MPE 中的积累预测患者生存率提高。这些数据为开发基于清除癌症患者这种细胞群的免疫增强策略提供了依据。
