Recurrent hepatocellular carcinoma cells with stem cell-like properties: possible targets for immunotherapy |
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| Authors: | Xiaolan Xu Baocai Xing Meihao Hu Zuoliang Xu Yong Xie Guanghai Dai Jun Gu Yu Wang Zhiqian Zhang |
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| Institution: | 1. National Key Laboratory of Protein Engineering and Plant Gene Engineering, Institute of Life Science, Peking University, Beijing, China;2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Beijing Cancer Hospital and Institute, School of Oncology, Peking University, Beijing, China;3. Department of Hepatobilliary Surgery I, Beijing Cancer Hospital and Institute, School of Oncology, Peking University, Beijing, China;4. Department of Biology, Hong Kong University of Science and Technology, Hong Kong, China;5. Department of Medical Oncology, General Hospital of the Chinese People''s Liberation Army, Beijing, China;1. UNSW Department of Surgery, St George Clinical School, University of New South Wales, Sydney, Australia;2. The Collaborative Research (CORE) Group, Sydney, Australia;1. Royal Brompton and Harefield NHS Foundation Trust, London, UK;2. National Heart and Lung Institute, Imperial College London, London, UK;1. Department of Chemical and Biochemical Engineering, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, 812 37 Bratislava, Slovak Republic;2. Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, 812 37 Bratislava, Slovak Republic;3. Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava, Slovak Republic;4. Institute of Virology, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 05 Bratislava, Slovak Republic;5. Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, Pavol Jozef ?afárik University, Moyzesova 11, 041 54 Ko?ice, Slovak Republic;3. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106;4. Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106;5. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106;9. Department of Cardiovascular Medicine, Case Western Reserve University, Cleveland, Ohio 44106;8. Department of Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106;6. Department of Center for Mitochondrial Disease, Case Western Reserve University, Cleveland, Ohio 44106;12. St. Vincent''s Clinical School and the School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales 2010, Australia |
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| Abstract: | Background aimsHepatocellular carcinoma (HCC) recurs with high frequency. Characterization of recurrent HCC cells will facilitate the design of future therapeutic strategies for recurrent HCC.MethodsTwo 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.ResultsCompared 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-α (TNF-α) and interferon-γ (IFN-γ) 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.ConclusionsOur 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-α and IFN-γ 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. |
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