title: Signaling pathways induced by a tumor-derived vaccine in antigen presenting cells.
abstract: We have previously reported on the anti-tumoral potential of a chaperone-rich cell lysate (CRCL) vaccine. Immunization with CRCL generated from tumors elicits specific T and NK cell-dependent immune responses leading to protective immunity in numerous mouse tumor models. CRCL provides both a source of tumor antigens and danger signals leading to dendritic cell activation. In humans, tumor-derived CRCL induces dendritic cell activation and CRCL-loaded dendritic cells promote the generation of cytotoxic T lymphocytes in vitro. The current study was designed to identify the signaling events and modifications triggered by CRCL in antigen presenting cells. Our results indicate that tumor-derived CRCL not only promotes the activation of dendritic cells, but also significantly fosters the function of macrophages that thus appear as major targets of this vaccine. Activation of both cell types is associated with the induction of the MAP kinase pathway, the phosphorylation of STAT1, STAT5 and AKT and with transcription factor NF-kappaB activation in vitro and in vivo. These results thus provide important insights into the mechanisms by which CRCL-based vaccines exert their adjuvant effects on antigen presenting cells.
authors.affiliation: Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cantrell
authors.forename: Claire
authors.initials: C
authors.lastname: Larmonier
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Sara
authors.initials: S
authors.lastname: Bustamante
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.forename: Amanda
authors.initials: A
authors.lastname: Herrell
authors.forename: Tamara
authors.initials: T
authors.lastname: Lundeen
authors.forename: Collin
authors.initials: C
authors.lastname: J LaCasse
authors.forename: Elaine
authors.initials: E
authors.lastname: Situ
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D019496:Cancer Vaccines; D002457:Cell Extracts / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D002457:Cell Extracts; D016212:Transforming Growth Factor beta; D051058:Oncogene Protein v-akt