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Cytokine-enhanced cytolytic activity of exosomes from NK Cells.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 2022 Jun; Vol. 29 (6), pp. 734-749. Date of Electronic Publication: 2021 Jul 27. - Publication Year :
- 2022
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Abstract
- Natural killer (NK) cells play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell-cell interaction with cell surface proteins and then attack target cells via multiple mechanisms. In addition, extracellular vesicles (EVs) derived from NK cells (NK-EVs), including exosomes, possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells. Major cytolytic granules, granzyme B and granzyme H, are enriched by IL-15 + IL-21 stimulation in NK-EVs; however, knockout experiments reveal those cytolytic granules are independent of enhanced cytotoxic capacity. To find out the key molecules, mass spectrometry analyses were performed with different cytokine conditions, no cytokine, IL-15, IL-21, or IL-15 + IL-21. We then found that CD226 (DNAM-1) on NK-EVs is enriched by IL-15 + IL-21 stimulation and that blocking antibodies against CD226 reduced the cytolytic activity of NK-EVs. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings elucidate the novel properties of NK-EVs and the mechanism of their incorporation into target cells.<br /> (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021.)
Details
- Language :
- English
- ISSN :
- 1476-5500
- Volume :
- 29
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 34316033
- Full Text :
- https://doi.org/10.1038/s41417-021-00352-2