title: Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines.
abstract: While multiple pathways of dendritic cell (DC) maturation result in transient production of IL-12, fully mature DCs show reduced ability to produce IL-12p70 upon a subsequent interaction with Ag-specific T cells, limiting their in vivo performance as vaccines. Such "DC exhaustion" can be prevented by the presence of IFNgamma during the maturation of human DCs (type-1-polarization), resulting in improved induction of tumor-specific Th1 and CTL responses in vitro. Here, we show that type-1 polarization of mouse DCs strongly enhances their ability to induce CTL responses against a model tumor antigen, OVA, in vivo, promoting the induction of protective immunity against OVA-expressing EG7 lymphoma. Interestingly, in contrast to the human system, the induction of mouse DC1s requires the participation of IL-4, a nominal Th2-inducing cytokine. The current data help to explain the previously reported Th1-driving and anti-tumor activities of IL-4, and demonstrate that type-1 polarization increases in vivo activity of DC-based vaccines.
authors.affiliation: Department of Surgery, Hillman Cancer Center, University of Pittsburgh, UPCI Research Pavilion, Room 1.46b, 5117 Center Avenue, Pittsburgh, PA 15213-1863, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Giermasz
authors.forename: Julie A
authors.initials: JA
authors.lastname: Urban
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Payal
authors.initials: P
authors.lastname: Watchmaker
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Cumberland
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016764:Cell Polarity; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008223:Lymphoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin