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Cancer Lett. 2017 Dec 28;411:182-190. doi: 10.1016/j.canlet.2017.09.022. Epub 2017 Sep 23.

Co-delivery of tumor-derived exosomes with alpha-galactosylceramide on dendritic cell-based immunotherapy for glioblastoma.

Author information

1
Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China.
2
Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba 277-8577, Japan.
3
Department of Radiology, Chinese PLA General Hospital, Beijing 100853, China.
4
Key Laboratory of Cancer Center, Chinese PLA General Hospital, Beijing 100853, China.
5
Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China.
6
Department of Skull Base Surgery Center, Otorhinolaryngology Head and Neck Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
7
Department of Clinical Laboratory, Weihai Municipal Hospital, Weihai 264200, China.
8
Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: xinguang_yu@263.net.
9
Key Laboratory of Cancer Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: tianyiliu08@hotmail.com.

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.

KEYWORDS:

Dendritic cells; Exosome; Glioblastoma multiforme; Immunotherapy; Invariant natural killer T cells

PMID:
28947140
DOI:
10.1016/j.canlet.2017.09.022
[Indexed for MEDLINE]

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