Co-delivery of tumor-derived exosomes with alpha-galactosylceramide on dendritic cell-based immunotherapy for glioblastoma.
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| Abstract |
Dendritic cell (DC) vaccine-based immunotherapy for glioblastoma multiforme (GBM) has shown apparent benefit in animal experiments and early-phase clinical trials, but the survival benefit is variable. In this work, we analyzed the mechanism of the potent antitumor immune response induced in vivo by tumor-associated antigen (TAA)-specific DCs with an invariant natural killer T (iNKT) cell adjuvant in orthotopic glioblastoma-bearing rats vaccinated with tumor-derived exosomes and α-galactosylceramide (α-GalCer) -pulsed DCs. Compared with traditional tumor lysate, exosomes were utilized as a more potent antigen to load DCs. iNKT cells, as an effective cellular adjuvant activated by α-GalCer, strengthened TAA presentation through their interaction with DCs. Co-delivery of tumor-derived exosomes with α-GalCer on a DC-based vaccine showed powerful effects in glioblastoma immunotherapy. This vaccine induced strong activation and proliferation of tumor-specific cytotoxic T lymphocytes, synergistically breaking the immune tolerance and improving the immunosuppressive environment.
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| Authors | Hongyu Liu, Ling Chen, Jialin Liu, Hengxing Meng, Rong Zhang, Lin Ma, Liangliang Wu, Songyan Yu, Fei Shi, Ying Li, Lijun Zhang, Lingxiong Wang, Shiyu Feng, Qi Zhang, Yaojun Peng, Qiyan Wu, Chunxi Liu, Xin Chang, Lin Yang, Yasushi Uemura, Xinguang Yu, Tianyi Liu |
| Journal | Cancer letters (Cancer Lett) Vol. 411 Pg. 182-190 (12 28 2017) ISSN: 1872-7980 [Electronic] Ireland |
| PMID | 28947140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2017 Elsevier B.V. All rights reserved. |
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