Gene expression profiling of Tumor and liver infiltrating NK cells from patients with Hepatocellular Carcinoma

Natural Killer (NK) cells play a central role in cell-mediated immune response to cancer. In previous studies number and function of NK-cells have been shown to be positively correlated with HCC outcome. In this study, we have performed a genetic expression analysis comparing mRNA expression by NK cells from tumor samples derived from HCC patients to NK cells infiltrating the liver counterpart and to NK cells in the normal liver as controls. The bioinformatic analysis has been completed by an immunophenotypic study, functional analysis and metabolic assessment of the infiltrating NK cells. It is known that NK cells may present functional defects in HCC patients however previous studies have not systematically address the molecular mechanisms associated with these defects by an unbiased genetic expression study. We have identified altered cellular pathways and hypothesized possible mechanisms that could be targeted for restoring an immune-protective NK cell response. Liver and tumor-infiltrating lymphocytes from 11 patients with HCC arising in Hepatitis C virus (HCV) infection and 6 patients undergoing liver resection for colorectal metastasis as control were stained with appropriate fluorescent antibodies, in order to distinguish NK-cells. RNA was purified from sorted NK-cells and amplified. cDNA was labeled and hybridized to Agilent microarrays.