Potential Therapeutic Value Of Dendritic Cells Loaded With Ny-Eso-1 Protein For The Immunotherapy Of Advanced Hepatocellular Carcinoma

NY-ESO-1 is one of the most immunogenic cancer-testis (CT) antigens. Cancer vaccine trials based on NY-ESO-1 are currently ongoing. Dendritic cells (DCs) are the most potent antigen-presenting cells. The immune functions of DCs in a number of tumors have been identified; however, the potential therapeutic value of DCs pulsed with NY-ESO-1 in hepatocellular carcinoma (HCC) has not been extensively investigated. The objectives of the present study were to evaluate T cell response following stimulation with DCs pulsed with the recombinant NY-ESO-1 protein (rESO) and to establish a correlation between NY-ESO-1 expression and clinicopathological features in HCC patients. DCs were generated with granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) from human peripheral blood mononuclear cells. A mixed T cell reaction with DCs loaded with recombinant NY-ESO-1 protein (rESO-DCs) was evaluated by MTT assay. T cell responses against HCC cell lines were analyzed by measuring lactate dehydrogenase (LDH) activity. The protein levels of NY-ESO-1 were detected by immunohistochemistry (IHC) in a tissue microarray (TMA) containing 190 HCC samples. NY-ESO-1 transcript abundance was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 54 out of the 190 HCC samples. The results revealed that mature DCs were induced and that rESO-DCs significantly stimulated T cell proliferation. The specific lysis of T cells stimulated with rESO-DCs was significantly higher in the NY-ESO-1-positive HCC cells compared with the NY-ESO-1-negative cells and the other controls (p<0.01). NY-ESO-1 was expressed in 15.8% (30/190)of the HCC samples, as shown by IHC and in 24.1% (13/54) of the samples, as shown by RT-PCR. The frequency of NY-ESO-1 expression was significantly higher in HCC patients with portal vein tumor thrombosis (24.6%) compared with those without thrombosis (11.2%, p=0.013). Our data suggest that DCs loaded with NY-ESO-1 protein stimulate antigen-specific T cell responses against HCC cells in vitro. NY-ESO-1 may thus be used as a potential target for immunotherapy in advanced HCC.