Cutting edge: differentiation of antitumor CTL in vivo requires host expression of Stat1.
Several lines of evidence suggest that an IFN-gamma-producing, Th1/Tc1 phenotype may be optimal for tumor rejection. Recent work has indicated that IFN signaling on tumor cells is important for protection against carcinogenesis. However, the potential involvement of IFN signaling among host immune cells has not been carefully examined. To this end, Stat1-deficient mice were employed as tumor recipients. In contrast to wild-type mice, Stat1-/- mice failed to reject immunogenic tumors and did not support regression of poorly immunogenic tumors when treated with an IL-12-based vaccine. T cells from immunized Stat1-/- mice produced 50% of the levels of IFN-gamma and lacked cytolytic activity compared with wild-type mice, and NK lytic activity also was not observed. Lack of cytolytic function correlated with a failure to up-regulate serine esterase activity. Thus, IFN-mediated signaling on host cells is required for the development of antitumor lytic effector cells.
Fallarino
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F
Department of Pathology, Department of Medicine, Section of Hematology/Oncology, University of Chicago, IL 60637, USA.
Gajewski
T F
TF
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D006084:Graft Rejection / Q000209:etiology / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D014162:Transfection / Q000276:immunology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014611:Vaccination
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12