title: Dendritic cell activation by combined exposure to anti-CD40 plus interleukin (IL)-12 and IL-18 efficiently stimulates anti-tumor immunity.
abstract: Despite as yet limited clinical effectiveness, dendritic cell (DC)-based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti-tumor immunity often depends on the induction of type 1 (T(H)1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce T(H)1 immunity [anti-CD40, interleukin (IL)-12, IL-18], with the aim to trigger a T(H)1 driven anti-tumor CTL response. When compared with untreated DC or DC treated with anti-CD40 alone, DC matured with anti-CD40 plus IL-12 and IL-18 expressed significantly more IFN-gamma and IL-12, induced enhanced CD8(+) T-cell proliferation, prolonged synaptic interaction with T cells and increased CD8(+) T-cell-mediated cytotoxicity. To analyse if these DC are able to induce efficient anti-tumor immunity, mice carrying a B16-OVA tumor were treated with tumor antigen (TA)-loaded DC that had been exposed to anti-CD40 or to anti-CD40 plus IL-12 and IL-18. Our data show that anti-CD40 plus IL-12 and IL-18 matured DC are superior to controls in retarding tumor growth. These data indicate that maturation of DC with anti-CD40 plus IL-12 and IL-18 potently stimulates the generation of an anti-tumor immune response and may lead to improved immunotherapeutic capacity of DC vaccination.
authors.affiliation: Department of Dermatology, University of Mainz, Mainz, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Balkow
authors.forename: Karin
authors.initials: K
authors.lastname: Loser
authors.forename: Mathias
authors.initials: M
authors.lastname: Krummen
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Tobias
authors.initials: T
authors.lastname: Rothoeft
authors.forename: Jenny
authors.initials: J
authors.lastname: Apelt
authors.forename: Andrea
authors.initials: A
authors.lastname: Tuettenberg
authors.forename: Carsten
authors.initials: C
authors.lastname: Weishaupt
authors.forename: Stefan
authors.initials: S
authors.lastname: Beissert
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019013:CD40 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019013:CD40 Antigens; D020382:Interleukin-18; D018664:Interleukin-12