Regulatory T cell and activated natural killer cell infiltration in hepatocellular carcinoma: immune cell profiling using the CIBERSORT

Background: Hepatocellular carcinoma (HCC) is understood to be an immunogenic tumor caused by chronic liver disease. Emerging research has indicated close interaction between various immune cells and tumor cells. Immunophenotyping, which has shown potential predictive value for the prognosis of various human malignancies, might allow responsive and non-responsive patients to be identified based on the extent and distribution of immune cell infiltration. Several novel immunotherapeutic approaches have been trialed and have shown promising efficacy. However, the efficacy of immunotherapies in HCC is limited by several factors. This study aimed to investigate tumor-infiltrating immune cells in HCC. Methods: Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) allows immune cell profiling analysis by deconvolution of gene expression microarray data. In this study, we analyzed the proportions of immune cells in 14 paired samples of HCC tissues obtained from GSE84402 in Gene Expression Omnibus (GEO) database. Results: In the 14 paired samples, HCC tissues showed significant infiltration by regulatory T cells (Tregs), activated natural killer (NK) cells, and M0 macrophages (P<0.001, P=0.007 and P=0.001, respectively), which were validated in CIBERSORT with the P value set at <= 0.05. In four paired samples identified from those selected by CIBERSORT, HCC tissues were found to have significant Treg and activated NK cell infiltration compared to non-tumor tissues (P=0.007 and P=0.015, respectively). Additionally, Pearson correlation analysis revealed Tregs to be positively correlated with activated NK cells (Correlation coefficient =0.41). Conclusions: HCC tumor tissues were markedly infiltrated by Tregs and activated NK cells, which should be considered as candidate therapeutic targets in HCC multidisciplinary treatments.