Abstract
Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1 and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators for patients. In this study, therefore, we measured galectin-1 and miR-22 expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T cells and the production of cytokines (IFN-η and IL-10) in HSCs co-cultured with T cells. And we used immunohistochemical staining to tested for correlation between galectin-1 expression, CD3 expression and clinicopathological features in 162 HCC patients. Our results showed that galectin-1 expression was much higher in Ca-HSCs than in N-HSCs. Overexpression of galectin-1 promoted HSC-induced T cell apoptosis and cytokine production (IFN-η and IL-10), while miR-22 expression inhibited it. Galectin-1 expression correlated negatively with miR-22 expression in HSCs. High galectin-1 and low CD3 expression levels were associated with poor prognosis in HCC patients. These results suggest that the immunosuppressive microenvironment promoted by HSC-derived galectin-1 in HCC can be inhibited by miR-22. Galectin-1 and miR-22 could potentially serve as prognostic markers and therapeutic targets in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary tumour in the liver and is one of the most common human cancers worldwide [1]
To test the proapoptotic effect of human Hepatic stellate cells (HSCs) against T cells, CD3+ T cells were co-cultured with N-HSCs at different ratios (HSC:T = 1:5, 1:10, and 1:20; T cells cultured alone served as a negative control)
Our results indicated that HSCs could promote tumour immune privilege and tumour progression through galectin-1 expression, while this function can be suppressed by miR-22
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary tumour in the liver and is one of the most common human cancers worldwide [1]. While galectin-1 is expressed in human HuH-7 cells, JHH-6 cells and tumour hepatocytes of human HCC tissue sections [14], galectin-1 levels in hepatocytes are significantly lower in HCC specimens than in normal liver and cirrhotic specimens [14, 15]. Galectin-1 levels in stromal cells are higher in HCC specimens than in normal liver and cirrhotic specimens [14, 15]. Endogenous galectin-1 plays a key role in tumour immune privilege due to its capacity to induce apoptosis in activated T cells [7], which is relatively similar to the immunomodulatory properties www.impactjournals.com/oncotarget of HSCs. galectin-1 expression has been detected in rat HSCs [16, 17]. We investigated whether human HSCs express galectin-1 and whether galectin-1 contributes to HSC-mediated immunomodulatory functions and tumour immune privilege in HCC
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