PMID- 24085111 OWN - NLM STAT- MEDLINE DCOM- 20140527 LR - 20131024 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 32 IP - 6 DP - 2013 Dec TI - Potential therapeutic value of dendritic cells loaded with NY‑ESO‑1 protein for the immunotherapy of advanced hepatocellular carcinoma. PG - 1366-72 LID - 10.3892/ijmm.2013.1510 [doi] AB - 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. FAU - Chen, Yuqing AU - Chen Y AD - Department of Pathology, Fujian Medical University, Fuzhou, Fujian 350004 P.R. China. FAU - Huang, Aimin AU - Huang A FAU - Gao, Meiqin AU - Gao M FAU - Yan, Yongqin AU - Yan Y FAU - Zhang, Wenmin AU - Zhang W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130927 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Antigens, Neoplasm) RN - 0 (CTAG1B protein, human) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Adult MH - Aged MH - Antigens, Neoplasm/*genetics/metabolism MH - Carcinoma, Hepatocellular/genetics/immunology/*pathology/*therapy MH - Cell Line, Tumor MH - Cell Proliferation MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*metabolism MH - Female MH - Flow Cytometry MH - Gene Expression Regulation, Neoplastic MH - Humans MH - *Immunotherapy MH - Liver Neoplasms/genetics/immunology/*pathology/*therapy MH - Male MH - Membrane Proteins/*genetics/metabolism MH - Middle Aged MH - Neoplasm Staging MH - RNA, Messenger/genetics/metabolism MH - T-Lymphocytes/cytology MH - Young Adult EDAT- 2013/10/03 06:00 MHDA- 2014/05/28 06:00 CRDT- 2013/10/03 06:00 PHST- 2013/06/20 00:00 [received] PHST- 2013/09/17 00:00 [accepted] PHST- 2013/10/03 06:00 [entrez] PHST- 2013/10/03 06:00 [pubmed] PHST- 2014/05/28 06:00 [medline] AID - 10.3892/ijmm.2013.1510 [doi] PST - ppublish SO - Int J Mol Med. 2013 Dec;32(6):1366-72. doi: 10.3892/ijmm.2013.1510. Epub 2013 Sep 27.