Interleukin-35 Play Tumor Promoting Roles in Hepatocellular Carcinoma

Abstract

Backgroud: A long-term hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)-35 is the newest member of the IL-12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL-35 in hepatocellular carcinoma (HCC) and the effect on local immune status. Methods: HCC transcriptome array data were downloaded from Gene Expression Omnibus. The bioinformatics analysis was performed by the BRB array tools and online Ingenuity Pathway Analysis software. The serum IL-35 level was detected by AimPlet bead-based immunoassay. In situ IL-35 expression detection was performed by immunohistochemical staining and western blot. Results: Our results showed that there were large amounts of IL-35 expressed in HCC serum and tumor tissues. IL-35 expression affects the transcript of thousands of genes, most of which correlated with T-cell immunity. This study proved that enhancement of regulatory T cells (Tregs) and impairment of cytolytic T cells are prominent effects of IL-35. Conclusions: Elevated IL-35 played critical roles in HCC patients through affecting the balance between Tregs and cytotoxic T cells. Dissection of the precise targets and the underlying molecular mechanisms will lead to alternative treatments for HCC patients.