title: Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.
abstract: Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4(+) and CD8(+) T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c(+) His48(-) MHC II(+) cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti-T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth.
authors.affiliation: Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.|Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Luis
authors.initials: L
authors.lastname: Ubillos
authors.affiliation: Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Teresa
authors.initials: T
authors.lastname: Freire
authors.affiliation: Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, Uruguay.|Clínica Quirúrgica 1, Hospital Pasteur, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Berriel
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.|Unidad de Biología Molecular, Institut Pasteur de Montevideo, Uruguay.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Chiribao
authors.affiliation: Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Chiale
authors.affiliation: Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.|Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, Uruguay.
authors.forename: María Florencia
authors.initials: MF
authors.lastname: Festari
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Andrea
authors.initials: A
authors.lastname: Medeiros
authors.affiliation: Servicio de Anatomía Patológica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mazal
authors.affiliation: Servicio de Anatomía Patológica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Mariella
authors.initials: M
authors.lastname: Rondán
authors.affiliation: Unidad de Biología Celular, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollati-Fogolín
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.|Unidad de Biología Molecular, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robello
authors.affiliation: Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.|Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, Uruguay.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Osinaga
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D019496:Cancer Vaccines; D002273:Carcinogens; D008770:Methylnitrosourea; D019813:1,2-Dimethylhydrazine
keywords: Trypanosoma cruzi; cancer; parasite; vaccination