Li Jieyu, Huang Shenglan, Zhou Zhifeng, Lin Wansong, Chen Shuping, Chen Mingshui, Ye Yunbin
School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China,
Laboratory of Immuno-Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, China,
Cancer Manag Res. 2018 Oct 29;10:4945-4957. doi: 10.2147/CMAR.S178326. eCollection 2018.
Dendritic cell (DC)-derived exosomes (Dexs) have been proved to induce and enhance antigen-specific T cell responses , and previous clinical trials have shown the feasibility and safety of Dexs in multiple human cancers. However, there is little knowledge on the efficacy of Dexs against hepatocellular carcinoma (HCC) until now.
In this study, human peripheral blood-derived DCs were loaded with recombinant adeno-associated viral vector (rAAV)-carrying alpha-fetoprotein () gene (rAAV/AFP), and high-purity Dexs were generated. Then naive T cells were stimulated with Dexs to investigate the specific T cell-mediated immune responses against HCC.
Our findings showed that Dexs were effective to stimulate naive T cell proliferation and induce T cell activation to become antigen-specific cytotoxic T lymphocytes (CTLs), thereby exhibiting antitumor 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 Dexs, which combine the advantages of DCs and cell-free vectors, are promising to completely, or at least in part, replace mature DCs (mDCs) to function as cancer vaccines or natural antitumor adjuvant.
树突状细胞（DC）来源的外泌体（Dexs）已被证明可诱导和增强抗原特异性T细胞反应，并且先前的临床试验已表明Dexs在多种人类癌症中的可行性和安全性。然而，迄今为止，关于Dexs对肝细胞癌（HCC）疗效的了解甚少。
在本研究中，用人外周血来源的DCs负载携带甲胎蛋白（AFP）基因的重组腺相关病毒载体（rAAV）（rAAV/AFP），并产生高纯度的Dexs。然后用Dexs刺激初始T细胞，以研究针对HCC的特异性T细胞介导的免疫反应。
我们的研究结果表明，Dexs可有效刺激初始T细胞增殖并诱导T细胞活化成为抗原特异性细胞毒性T淋巴细胞（CTLs），从而表现出针对HCC的抗肿瘤免疫反应。此外，Dex致敏的DC前体似乎更有效地触发主要组织相容性复合体I类（MHC I）限制的CTL反应，并使DCs充分利用次要抗原肽，从而最大程度地激活针对HCC的特异性免疫反应。
得出结论，结合了DCs和无细胞载体优势的Dexs有望完全或至少部分替代成熟DCs（mDCs），作为癌症疫苗或天然抗肿瘤佐剂发挥作用。
