Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Innate and adaptive immunity to tumors: IL-12 is required for optimal responses

P Grufman, K Karre

1 Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden,

AIMS: To investigate the role for endogenously produced IL-12 in immunity against tumors. METHODS: To investigate the role for IL-12 in adaptive immunity mice were immunized with irradiated tumor cells, dendritic cells loaded with synthetic peptides or synthetic peptides in adjuvant. Following immunization B6 and IL-12 deficient mice were inoculated with live tumor cells and followed for several weeks. We also compared the cytotoxic ability after restimulation in vitro. Innate immune responses were studied by inoculating wildtype and IL-12 deficient mice with TAP deficient tumor cells and by comparing in vitro cytotoxicity by tilorone activated NK cells. RESULTS: Endogenously produced IL-12 was crucial for the immunity induced by one immunization with irradiated RMA cells. This defect could be overcome by multiple immunizations. In further studies of in vitro CTL responses, we found that IL-12 production from either the antigen pulsed dendritic cells or from host cells was necessary to obtain strong CTL responses. In the complete absence of IL-12, no or only very weak responses could be detected. NK cell mediated innate resistance, as assessed in non-immunized mice inoculated with a threshold dose of RMA-S cells, also required IL-12. However, NK cells with reduced activity were present in IL-12 deficient mice and contributed to innate resistance, as demonstrated with lower cell dose challenges. CONCLUSIONS: IL-12 is not absolutely required for adaptive or innate immunity against tumors, but it seems to be essential for an optimal, early response.

KEY WORDS: Dendritic cells, .

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.