Molecular mechanisms underlying IFN-γ-mediated tumor growth inhibition induced during tumor growth inhibition induced during tumor immunotherapy with rIL-12

摘要: The present study investigates the molecular mechanisms by which IFN-gamma produced as a result of in vivo IL-12 administration exerts its anti-tumor effects. rIL-12 was administered three or five times into mice bearing CSA1M fibrosarcoma, OV-HM ovarian carcinoma MCH-1-A1 fibrosarcoma. This regimen induced complete regression and tumors but only transient growth inhibition tumors. effects were associated with enhanced induction because these abrogated pretreatment hosts anti-IFN-gamma antibody. Exposure vitro types tumor cells to rRFN-gamma resulted moderate potent cell growth. stimulated expression mRNAs for an inducible type NO synthase (iNOS) indoleamine 2,3-dioxygenase (IDO), enzyme capable degrading tryptophan, OH-HM cells, marginal levels cells. In association iNOS gene expression, IFN-gamma-stimulated large amount functioned inhibit their own vitro. Although MCH-1A1 did not produce NO, they also exhibited susceptibility. Whereas masses from IL-12-treated CSA1M-bearing OV-HM-bearing higher (for CSA1M) IDO OV-HM) mRNAs, mass expressed lower mRNA alone. Moreover, massive infiltration CD4(+) CD8(+) T Mac-1(+) seen Thus, results indicate that after treatment induces various genes potential modulate acting directly on stimulating tumor-infiltrating lymphoid effectiveness therapy is operation mechanisms.