Xenogenization of tumor cells by fusogenic exosomes in tumor microenvironment ignites and propagates antitumor immunity
- Xenogenization of tumor cells by fusogenic exosomes in tumor microenvironment ignites and propagates antitumor immunity
- 권익찬; 우지완; 김인산; 양유수; 조약돌; 남기훈; 김기범; 홍연선
- Issue Date
- Science Advances
- VOL 6, NO 27, eaaz2083
- 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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