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Dendritic cell activation by combined exposure to anti‐CD40 plus interleukin (IL)‐12 and IL‐18 efficiently stimulates anti‐tumor immunity
Author(s) -
Balkow Sandra,
Loser Karin,
Krummen Mathias,
Higuchi Tetsuya,
Rothoeft Tobias,
Apelt Jenny,
Tuettenberg Andrea,
Weishaupt Carsten,
Beissert Stefan,
Grabbe Stephan
Publication year - 2009
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00800.x
Subject(s) - cd40 , dendritic cell , immune system , cd8 , interleukin 15 , immunology , immunity , immunotherapy , t cell , tumor antigen , cytotoxic t cell , ctl* , interleukin 12 , cancer research , interleukin 4 , cancer immunotherapy , acquired immune system , cellular immunity , biology , interleukin , cytokine , in vitro , biochemistry
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‐γ 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.