Tan Hongwu, Wang Shuyun, Zhao Ludong
Department of Gastroenterology, Linyi People's Hospital, Shandong, China.
Operation Room, Linyi People's Hospital, Shandong, China.
Clin Exp Pharmacol Physiol. 2017 Feb;44(2):213-221. doi: 10.1111/1440-1681.12689.
Hepatocellular carcinoma (HCC) is a common and aggressive human malignancy. An imperative demand is present for a better understanding of the functions and regulations of the immune system and how they affect HCC pathogenesis. Recently, a group of interleukin 9 (IL-9)-producing CD4 T cells, termed Th9 cells, has been described in mice and humans with both tumour-inhibiting as well as tumour-promoting effects. The specific roles of Th9 cells in human HCC are not entirely understood. Here, we examined the frequencies and functions of IL-9-producing Th9 cells in HCC patients. We found that the frequencies of circulating IL-9-producing Th9 cells were significantly higher in HCC patients compared to in healthy individuals. In HCC patients, the frequencies of IL-9-producing Th9 cells were significantly higher in peritumour and tumour tissues than in unaffected liver tissues. Interestingly, HCC patients with higher tumour-infiltrating Th9 frequency had significantly shorter disease-free survival period after resection. Previously, high expression of CCL20 was associated with poor prognosis in HCC. CCL20 also induced epithelial-mesenchymal transition-like changes in HCC cells. We found that incubation of primary HCC cells with autologous Th9 significantly elevated the CCL20 production from tumour cells, which could be partially inhibited by suppressing STAT3. Together, this study suggested a tumour-promoting role of Th9 cells in HCC.
肝细胞癌（HCC）是一种常见且侵袭性强的人类恶性肿瘤。目前迫切需要更好地了解免疫系统的功能和调控机制，以及它们如何影响HCC的发病机制。最近，在小鼠和人类中都发现了一组产生白细胞介素9（IL-9）的CD4 T细胞，称为Th9细胞，它们具有肿瘤抑制和肿瘤促进双重作用。Th9细胞在人类HCC中的具体作用尚未完全明确。在此，我们检测了HCC患者中产生IL-9的Th9细胞的频率和功能。我们发现，与健康个体相比，HCC患者循环中产生IL-9的Th9细胞频率显著更高。在HCC患者中，肿瘤周围和肿瘤组织中产生IL-9的Th9细胞频率明显高于未受影响的肝组织。有趣的是，肿瘤浸润Th9细胞频率较高的HCC患者在切除术后无病生存期明显更短。此前，CCL20的高表达与HCC的不良预后相关。CCL20还可诱导HCC细胞发生上皮-间质转化样变化。我们发现，将原发性HCC细胞与自体Th9细胞共同孵育可显著提高肿瘤细胞CCL20的产生，而抑制STAT3可部分抑制这一过程。综上所述，本研究提示Th9细胞在HCC中具有促进肿瘤的作用。
