Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.
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2016
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info:eu-repo/semantics/altIdentifier/doi/10.1038/cddis.2016.134
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info:eu-repo/semantics/altIdentifier/pmid/27253407
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_EBCCD2380B139
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A. Gomez-Cadena et al., « Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model. », Serveur académique Lausannois, ID : 10.1038/cddis.2016.134
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Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells.