Antitumor immunity induced by dendritic cell-based vaccination is dependent on interferon-gamma and interleukin-12 |
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Authors: | Hiramoto Jade S Tsung Kangla Bedolli Melanie Norton Jeffrey A Hirose Ryutaro |
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Affiliation: | Department of Surgery, University of California, San Francisco, California 94143-0780, USA. HiroseR@surgery.ucsf.edu |
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Abstract: | BACKGROUND: This study was conducted to determine whether dendritic cells (DCs) pulsed with a tumor cell lysate can effectively vaccinate against tumor cells and to establish which cytokines are necessary. MATERIALS AND METHODS: Each wild-type mouse received two subcutaneous immunizations (days 14 and 7) with either saline, tumor lysate, DCs, or tumor-lysate-pulsed DCs. Gamma-interferon (gamma-IFN), knock-out (KO), and interleukin-12 (IL-12) KO mice were also used in immunizations. A tumor challenge was given at day 0. Splenocytes were assayed for gamma-IFN production. RESULTS: All saline-injected mice (n = 19) and all mice injected with tumor lysate (n = 9) developed tumors. Six of nine mice immunized with DCs alone and 6/24 mice treated with lysate-pulsed DCs developed a tumor. Splenocytes from both the saline- and lysate-immunized groups produced undetectable levels of gamma-IFN, while those from mice immunized with either DCs or pulsed DCs produced high levels of gamma-IFN. Four of five gamma-IFN KO mice developed tumors after immunization with tumor-lysate-pulsed DCs. None of four IL-12 KO mice developed a tumor after immunization with wild-type pulsed DCs and 1/10 wild-type mice developed tumor after immunization with IL-12 KO pulsed DCs. Three of four IL-12 KO mice developed tumors after immunization with IL-12 KO pulsed DCs. CONCLUSIONS: Tumor-lysate-pulsed DCs can initiate an effective antitumor immune response. The presence of gamma-IFN in the host is essential for antitumor protection. In contrast, tumor protection is observed if IL-12 is present in either the host or the DCs. |
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Keywords: | dendritic cell tumor vaccine IL-12 interferon-γ |
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