Xenogenization of tumor cells by fusogenic exosomes in tumor microenvironment ignites and propagates antitumor immunity
- Authors
- Kim, Gi Beom; Nam, Gi-Hoon; Hong, Yeonsun; Woo, Jiwan; Cho, Yakdol; Kwon, Ick Chan; Yang, Yoosoo; Kim, In-San
- Issue Date
- 7월-2020
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Citation
- SCIENCE ADVANCES, v.6, no.27
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENCE ADVANCES
- Volume
- 6
- Number
- 27
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/54839
- DOI
- 10.1126/sciadv.aaz2083
- ISSN
- 2375-2548
- Abstract
- Many cancer patients not responding to current immunotherapies fail to produce tumor-specific T cells for various reasons, such as a lack of recognition of cancer cells as foreign. Here, we suggest a previously unidentified method for xenogenizing (turning self to non-self) tumors by using fusogenic exosomes to introduce fusogenic viral antigens (VSV-G) onto the tumor cell surface. We found that xenogenized tumor cells were readily recognized and engulfed by dendritic cells; thereby, tumor antigens were efficiently presented to T lymphocytes. Moreover, exosome-VSV-G itself acts as a TLR4 agonist and stimulates the maturation of dendritic cells, leading to CD8(+) T cell cross-priming. The administration of these exosomes in multiple tumor mouse models xenogenized tumor cells, resulting in tumor growth inhibition. The combinatorial treatment with anti-PD-L1 exhibited complete tumor regression (30%) and better long-term overall survival. These results suggest that tumor xenogenization by fusogenic exosomes provides a previously unidentified a novel strategy for cancer immunotherapy.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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