A tumour-promoting role of Th9 cells in hepatocellular carcinoma through CCL20 and STAT3 pathways.

Abstract

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.