title: Induction of antigen-specific TH 9 immunity accompanied by mast cell activation blocks tumor cell engraftment.
abstract: The engraftment of circulating cancer cells at distal sites represents a key step in the metastatic cascade, yet remains an unexplored target for therapeutic intervention. In this study, we establish that a vaccination strategy yielding an antigen-specific TH 9 response induces long term host surveillance and prevents the engraftment of circulating cancer cells. Specifically, we show that vaccination with a recombinant CEA IgV-like N domain, formulated with the TLR3 ligand poly I:C, elicits a CEA-specific TH 9 response, wherein IL-9 secreting TH cells act in concert with CEA N domain-specific antibodies as well as activated mast cells in preventing tumor cell engraftment. The development of this immune response was dependent on TLR3, since interference with the TLR3-dsRNA complex formation led to a reduction in vaccine-imparted protection and a shift in the resulting immune response toward a TH 2 response. These findings point to the existence of an alternate tumor targeting immune mechanism that can be exploited for the purpose of developing vaccine therapies targeting tumor dissemination and engraftment.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.
authors.forename: Aws
authors.initials: A
authors.lastname: Abdul-Wahid
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.
authors.forename: Marzena
authors.initials: M
authors.lastname: Cydzik
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Prodeus
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.|Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Mays
authors.initials: M
authors.lastname: Alwash
authors.affiliation: Division of Plastic Surgery Department of Surgery, University of Toronto, ON, Canada.
authors.forename: Mile
authors.initials: M
authors.lastname: Stanojcic
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.
authors.forename: Megan
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.
authors.forename: Eric H-B
authors.initials: EH
authors.lastname: Huang
authors.affiliation: Department of Immunology, Beckman Research Institute, City of Hope, Duarte, CA.
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gray-Owen
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Physical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA.|Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Gariépy
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D016906:Interleukin-9 / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D016906:Interleukin-9; D051196:Toll-Like Receptor 3
keywords: TH9 immunity; cancer vaccine; metastatic dissemination; toll-like receptor 3; tumor cell engraftment