PMID- 19929456 OWN - NLM STAT- MEDLINE DCOM- 20100519 LR - 20180629 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 12 IP - 2 DP - 2010 Apr TI - Recurrent hepatocellular carcinoma cells with stem cell-like properties: possible targets for immunotherapy. PG - 190-200 LID - 10.3109/14653240903390803 [doi] AB - BACKGROUND AIMS: Hepatocellular carcinoma (HCC) recurs with high frequency. Characterization of recurrent HCC cells will facilitate the design of future therapeutic strategies for recurrent HCC. METHODS: Two cell lines, Hep-11 and Hep-12, were established from the same HCC patient's primary and recurrent tumor tissues, respectively, and then analyzed for stem cell-like properties, immune evasion strategies and immunogenicity. RESULTS: Compared with Hep-11 cells, Hep-12 cells expressed higher levels of liver progenitor cell makers and displayed persistent tumorigenic potential in the serial transplantation assay. Although Hep-12 cells down-regulated human leukocyte antigen (HLA) class I expression, they could still be recognized and killed by autologous-activated tumor-infiltrating lymphocytes (TIL) in vitro. Pre-treatment with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) increased the expression of HLA class I molecules on Hep-12 cells, and rendered them more susceptible to CD8(+) T-cell-mediated recognition and TIL-mediated cytotoxicity in vitro. CONCLUSIONS: Our results indicate that Hep-12 cells possess stem cell-like properties, are susceptible to autologous-activated TIL-mediated recognition and cytotoxicity, and pre-treatment with TNF-alpha and IFN-gamma enhances their immunogenicity. This is the first evidence to support the hypothesis that immunotherapy can be used to target recurrent HCC cells with stem cell-like properties. This strategy may be an effective therapeutic approach to prevent HCC recurrence and control recurrent HCC growth. FAU - Xu, Xiaolan AU - Xu X AD - National Key Laboratory of Protein Engineering and Plant Gene Engineering, Institute of Life Science, Peking University, Beijing, China. FAU - Xing, Baocai AU - Xing B FAU - Hu, Meihao AU - Hu M FAU - Xu, Zuoliang AU - Xu Z FAU - Xie, Yong AU - Xie Y FAU - Dai, Guanghai AU - Dai G FAU - Gu, Jun AU - Gu J FAU - Wang, Yu AU - Wang Y FAU - Zhang, Zhiqian AU - Zhang Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Biomarkers, Tumor) RN - 0 (Lysosomal-Associated Membrane Protein 1) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Biomarkers, Tumor/metabolism MH - CD8-Positive T-Lymphocytes/immunology MH - Carcinoma, Hepatocellular/immunology/*pathology/prevention & control/*therapy MH - Cell Death MH - Cell Line, Tumor MH - Enzyme Assays MH - Humans MH - Immune Evasion/immunology MH - *Immunotherapy MH - Killer Cells, Natural/immunology MH - L-Lactate Dehydrogenase/metabolism MH - Liver Neoplasms/pathology/*prevention & control/*therapy MH - Lymphocyte Activation/immunology MH - Lymphocytes, Tumor-Infiltrating/immunology MH - Lysosomal-Associated Membrane Protein 1/metabolism MH - Male MH - Middle Aged MH - Neoplastic Stem Cells/immunology/*pathology MH - Recurrence MH - Xenograft Model Antitumor Assays EDAT- 2009/11/26 06:00 MHDA- 2010/05/21 06:00 CRDT- 2009/11/26 06:00 PHST- 2009/11/26 06:00 [entrez] PHST- 2009/11/26 06:00 [pubmed] PHST- 2010/05/21 06:00 [medline] AID - S1465-3249(10)70381-9 [pii] AID - 10.3109/14653240903390803 [doi] PST - ppublish SO - Cytotherapy. 2010 Apr;12(2):190-200. doi: 10.3109/14653240903390803.