Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma

Background/Aims Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. It is expressed in normal tissues, and enhanced expression in many cancers has been reported. In this study, we investigated the usefulness of MRP3 as a target antigen in immunotherapy for hepatocellular carcinoma (HCC). Methods The MRP3 expression level in HCC tissue was measured by quantitative PCR. MRP3-specific T cell responses were investigated by several immunological techniques using peripheral blood mononuclear cells or tumor-infiltrating lymphocytes. Results The MRP3 expression level in HCC tissue was significantly higher than that in non-cancerous tissue (P < 0.05). MRP3-specific cytotoxic T cells (CTLs) could be induced regardless of liver function, the presence or absence of HCV infection, the blood AFP level, and the stage of HCC. The CTLs showed cytotoxicity against HCC cells overexpressing MRP3. A negative correlation was present between the MRP3 expression level in HCC tissue and the frequency of MRP3-specific CTLs. The frequency of MRP3-specific CTLs increased after HCC treatment, such as transcatheter arterial embolization and radiofrequency ablation. Conclusions Our study demonstrates that MRP3 is a potential candidate for tumor antigen with strong immunogenicity in HCC immunotherapy.