Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma
Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from c...
| Main Authors: | , , , , , , , , |
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
| Published: |
Elsevier
2019
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.12123/4586 https://www.sciencedirect.com/science/article/pii/S0264410X19301872?via%3Dihub https://doi.org/10.1016/j.vaccine.2019.02.004 |
| Summary: | Exosomes are 60–150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derived
exosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greater
immunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells is
limited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxic
drugs, hypoxia, acidosis, or radiation by increasing the release of EVs.
In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantly
increased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, and
CD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolated
from LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence
of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected
against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cells
were induced in immunized mice and a specific cytotoxic cellular immune response was elicited
in vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs.
Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhance
the secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may be
used to produce antigens for future design of cancer vaccines. |
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