Stat1 deficiency in the host enhances interleukin-12-mediated tumor regression

Cancer Research
Marina N TorreroShulin Li

Abstract

Signal transducer and activator of transcription 1 (Stat1) is considered a key transcription factor that inhibits tumorigenesis, and Stat1 activation in the host is required for interleukin-12 (IL-12)-mediated generation of CTL activity. Using syngeneic Stat1-/- C3H mice bearing SCCVII tumors in this study, we discovered opposite results. Stat1 deficiency in the host significantly enhances IL-12-mediated tumor regression, resulting in tumor eradication from 60% of SCCVII tumor-bearing mice and significant inhibition of tumor growth when compared with control treatment (P < 0.01). This effect is independent of both Stat1-activating cytokine IFN-gamma and Stat1-downstream effector molecule FasL because neither neutralization of IFN-gamma nor knocking out of FasL enhances or inhibits IL-12-mediated tumor regression. IL-12 induces a high intensity of tumor-specific CTL activity in Stat1-deficient mice (P < 0.01), increases the CD8 T-cell density in tumor bearing Stat1-/- mice, and induces a T-cell-dependent tumor regression. The increased CTL activity and the high-intensity infiltration of T cells into the tumors in IL-12-treated Stat1-/- mice are likely due to the longer survival than the same cells from wild-type mice. Together, ...Continue Reading

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Citations

Apr 7, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Song-Nan ZhangChae-Ok Yun
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