Exosomes derived from rAAV/AFP-transfected dendritic cells elicit specific T cell-mediated immune responses against hepatocellular carcinoma
作者单位：School of Basic Medical SciencesFujian Medical University Laboratory of Immuno-OncologyFujian Cancer Hospital & Fujian Medical University Cancer Hospital Fujian Key Laboratory of Translational Cancer Medicine
会议名称：《2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青...》
会议日期：2017年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：Hepatocellular carcinoma Dendritic cell Exosome Immune response Cytotoxic T lymphocyte
摘 要：Dendritic cell（DC）-derived exosomes（Dex） have been proved to induce and enhance antigen-specific T cell responses in vivo, and previous clinical trials have shown the feasibility and safety of Dex in multiple human cancers. However, there is little knowledge on the efficacy of Dex against hepatocellular carcinoma（HCC） until now. In this study, human peripheral blood-derived DCs were loaded with recombinant adenoassociated viral vector（r AAV） carrying alpha-fetoprotein（AFP） gene（rAAV/AFP）, and high-purity Dex were generated. Then, na?ve T cells were stimulated with Dex, to investigate the specific T cell-mediated immune responses against HCC. Our findings showed that Dex were effective to stimulate na?ve T cell proliferation, and induce T cell activation to become antigen-specific cytotoxic T lymphocytes（CTLs）, thereby exhibiting anti-tumor immune responses against HCC. In addition, Dex-sensitized DC precursors seemed more effective to trigger major histocompatibility complex class I（MHC I）-restricted CTL response and allow DCs to make full use of the minor antigen peptides, thereby maximally activating specific immune responses against HCC. It is concluded that Dex, which combine the advantages of DCs and cell-free vectors, are promising to completely, or at least in part, replace mature DCs to function as cancer vaccines or natural antitumor adjuvant.