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.