We have demonstrated previously that established small and large murine MCA207 sarcomas can be completely eradicated by treatment with interleukin (IL) 12 alone and cyclophosphamide plus IL-12 (Cy+IL-12), respectively. The antitumor effect of IL-12/Cy+IL-12 has been found to be dependent on IFN-gamma and T cells. The role of IFN-gamma in IL-12-induced tumor rejection is unclear, because after IL-12 administration IFN-gamma is produced by multiple cell types, and it acts on most cell types because of the ubiquitous expression of its receptor. Using a T-cell-adoptive transfer model, we show that after IL-12 treatment, tumor-specific T-cell production of IFN-gamma is necessary and sufficient for rejection of established tumors. Furthermore, by testing tumors using IFN-gamma-unresponsive tumor cells, we show that tumor cell expression of MHC class I molecules in vivo is abrogated by blocking the response to IFN-gamma. However, tumor response to IFN-gamma is not essential for rejection of established small and large tumors by IL-12 and Cy+IL-12, respectively; neither is it essential for expression of tumor immunogenicity. Our results indicate that the rejection of established tumors by IL-12/Cy+IL-12 is dependent on the induction of a Th1 response producing IFN-gamma that acts on host cells.
View details for Web of Science ID 000177496600029
View details for PubMedID 12183428