Potential therapeutic value of dendritic cells loaded with NY‑ESO‑1 protein for the immunotherapy of advanced hepatocellular carcinoma

Chen,Yuqing; Huang,Aimin; Gao,Meiqin; Yan,Yongqin; Zhang,Wenmin

doi:10.3892/ijmm.2013.1510

Potential therapeutic value of dendritic cells loaded with NY‑ESO‑1 protein for the immunotherapy of advanced hepatocellular carcinoma

Authors:
- Yuqing Chen
- Aimin Huang
- Meiqin Gao
- Yongqin Yan
- Wenmin Zhang
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Affiliations: Department of Pathology, Fujian Medical University, Fuzhou, Fujian 350004 P.R. China
Published online on: September 27, 2013 https://doi.org/10.3892/ijmm.2013.1510
Pages: 1366-1372

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Abstract

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.

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