A Novel Potential Strategy for Enhancing Antigen Presentation of Human Hepatocellular Carcinoma Cells Propagated ex-vivo Using a Ribonuclease Enzyme System

Hepatocellular carcinoma (HCC) is considered a major health problem as it is the fifth most common neoplasm in the world. It represents one of the most resistant types of malignancy, as systemic therapy with cytotoxic drugs provides only marginal benefits, especially with advanced stages. Dendritic cells-based immunotherapy may represent a novel and effective tool for HCC treatment. The current study was designed to investigate the possible enhancement of antigen presentation following treatment of HCC cancer cells ex-vivo using ribonuclease A (RNase A). Activated lymphocytes and monocytes-derived dendritic cells isolated from HCC patients were pulsed by RNase A- and/or sorafenib-treated autologous HCC cells. The expression of genes involved in antigen presentation, including LMP-2 and TAP-2, and some immunophenotypic markers in different phases of the immune response were evaluated. Treatment of HCC cells with RNase A caused a significant enhancement of antigen presentation, as demonstrated by the upregulation of LMP-2 and TAP-2 mRNA gene expressions, augmented T-lymphocytes priming by dendritic cells (as revealed by the upregulation of CD44 mRNA gene expression), that ultimately exaggerated the immune response. Our findings indicate that RNase A-treated HCC cells exhibited a better presentation of tumor associated antigens. Further studies are recommended to elucidate the underlying contributory mechanisms involved in HCC attenuation by RNases.