已有报告发现由白细胞介素9（IL-9）介导产生的CD4+T细胞（Th9细胞）参与了炎症和免疫性疾病的发病过程。然而，有关Th9细胞与恶性肿瘤的关系尚缺乏研究。为了阐明Th9细胞在恶性胸腔积液（MPE）中的分化机制，并探讨Th9细胞对肺癌细胞的免疫调节 style=color:blue >免疫调节作用，来自于中国武汉市华中科技大学同济医学院附属协和医院、卫生部肺部疾病重点实验室、呼吸和危重症医学科的叶志坚及其同事开展了一项研究，研究结果发表于2012年12月1日出版的《美国呼吸与危重症医学》（ Am. J. Respir. Crit. Care Med）杂志上。研究结果显示：恶性胸腔积液中的Th9细胞数量增加，Th9细胞在人类的肿瘤环境中对肺癌细胞的增殖、凋亡、和迁移活动发挥了重要的免疫调节作用。

研究者测定了患者血液及恶性胸腔积液中Th9细胞及相关的Th17细胞和Th1细胞的分布状况。并探讨了促炎性细胞因子和调节T细胞在体外对Th9细胞分化的影响及其影响机制。研究者同时还对白细胞介素-9、白细胞介素-17、和干扰素-γ对肺癌细胞株的影响和信号转导等进行了研究。

研究结果显示，与血液中相比，患者恶性胸腔积液中Th9细胞及相关的Th17细胞和Th1细胞的数量均有增加。而恶性胸腔积液中Th9细胞的增加是由细胞因子和调节T细胞的促进作用引起的。通过激活转录信号转导子与激活子3（STAT3）信号，Th 9细胞及Th17细胞都大大促进了肺癌细胞的增殖和迁移活动，而能够激活转录信号转导子与激活子1（STAT1）信号的干扰素-γ，则被发现能抑制肺癌细胞的增殖和迁移，并能诱导肺癌细胞凋亡。此外，白细胞介素-9和干扰素-γ（但不包括白细胞介素-17）还可以强烈促进肺癌细胞对单层胸膜间皮细胞的细胞间粘附能力。

该研究结果表明，恶性胸腔积液中的Th 9细胞数量增加，Th9细胞在人类的肿瘤环境中，对肺癌细胞的增殖、凋亡、和迁移活动发挥了重要的免疫调节作用。

与肺癌相关的拓展阅读：

• NAT GENET ：亚洲不吸烟妇女为何易患肺癌？
• Th9细胞对肺癌细胞的免疫调节
• CHEST：非小细胞肺癌I期患者行亚肺叶切除术易复发
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Differentiation and Immune Regulation of IL-9−Producing CD4⁺ T Cells in Malignant Pleural Effusion

Rationale

IL-9–producing CD4⁺ T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated.

Objectives

To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells.

Methods

Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated.

Measurements and Main Results

The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers.