Carcinogenesis, Teratogenesis & Mutagenesis ›› 2019, Vol. 31 ›› Issue (1): 29-34.doi: 10.3969/j.issn.1004-616x.2019.01.005

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Stimulation of dendritic cell-mediated antitumor tumor effect from HepG2 cell exosomes

ZHANG Ju, YE Shulai, ZHANG Changlong, ZHOU Qian   

  1. Department of Clinical Laboratory, the First Affiliated Hospital of University of Science and Technology of China/Anhui Provincial Hospital, Hefei 230001, Anhui, China
  • Received:2018-09-19 Revised:2018-12-17 Online:2019-01-31 Published:2019-01-31

Abstract: OBJECTIVE:To investigate the liver cancer cell HepG2-dervied immunogenic substances as tumor antigens for dendritic cell-(DC) based immunotherapy of liver cancer. METHODS:Changes in morphology and protein expression of HepG2 cells were determined by transmission electron microscopy and western blot,respectively; and in surface molecules of DCs by flow cytometry using exosomes with a final concentration of 8 μg/mL. In addition,exosome-pulsed DCs were co-cultured with T lymphocytes for 5 days. Proliferation of lymphocytes was detected by CSFE staining,and their killing of tumors was detected by Annexin-V/PI double staining. RESULTS:The hepatoma cell HepG2 exosomes expressed the marker proteins CD63 and CD81,carried a large number of tumor antigens AFP and heat shock proteins HSP70 and HSP90,but did not express the cellular protein calnexin. Compared with the DC-MOCK group,exosome-pulsed DCs up-regulated the expression of surface molecules such as CD83,CD80,and CD86; promoted T lymphocyte proliferation (P < 0.01),and increased T cell-mediated tumor-specific and non-specific killing effects (P < 0.01). CONCLUSION:Hepatoma cell HepG2 exosomes carried a large number of tumor antigens and stimulated the maturation of DCs,which may serve as a potential antigenic spectrum of DCs-based immunotherapy for liver and other cancers.

Key words: exosomes, hepatocellular carcinoma, dendritic cells, HepG2 cells

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