title: Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.
abstract: 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.
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.|Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Gomez-Cadena
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: C
authors.initials: C
authors.lastname: Urueña
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: K
authors.initials: K
authors.lastname: Prieto
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Usatorre
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Donda
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: A
authors.initials: A
authors.lastname: Barreto
authors.affiliation: Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Romero
authors.affiliation: Grupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: S
authors.initials: S
authors.lastname: Fiorentino
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015415:Biomarkers; D037282:Calreticulin; D010936:Plant Extracts; D059808:Polyphenols; D004317:Doxorubicin; D053148:Caspase 3; D053453:Caspase 9