Cutting edge: spontaneous rejection of poorly immunogenic P1.HTR tumors by Stat6-deficient mice.
Experimental evidence suggests that a type 1 T cell response may result in optimal tumor rejection in vivo. This phenotype is determined in part by cytokines that influence T cell differentiation. In transplantable tumor models such as P1.HTR, tumors grow progressively despite expression of defined tumor Ags. We hypothesized that this failure to reject may be due to poor generation of a type 1 phenotype, through a dominant influence of the type 2-promoting cytokines IL-4 and/or IL-13. This hypothesis was tested by implanting P1.HTR tumors into mice deficient in Stat6. In contrast to progressive growth of P1.HTR tumors in wild-type mice, and aggressive growth even of IL-12-transfected P1.HTR in Stat1(-/-) mice, P1.HTR was spontaneously rejected by Stat6(-/-) mice. Rejection was accompanied by augmented tumor-specific IFN-gamma production and CTL activity. These results suggest that pharmacologic inhibition of Stat6 signaling could potentiate anti-tumor immunity in vivo.
Kacha
A K
AK
Department of Pathology and the Committee on Immunology, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Fallarino
F
F
Markiewicz
M A
MA
Gajewski
T F
TF
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics; D007939:Leukemia L1210; D012515:Mast-Cell Sarcoma / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; C494080:Stat1 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D007371:Interferon-gamma