Endogenous interferon-gamma acts directly on tumor cells in vivo to suppress growth.
BACKGROUND
Recent evidence implicates endogenous interferon-gamma (IFN-gamma) in the host response to an immunogenic tumor (MCA105); antibody blockade of host IFN-gamma increased tumor growth rate (Doherty et al., Ann. Surg. Oncol. 3: 198-203, 1996). Those experiments did not attempt to determine the site of IFN-gamma activity (the host, the tumor, or both).


METHODS
MCA101 murine tumor cells were transfected with a plasmid expression vector containing an antisense construct to the IFN-gamma receptor (IFN-gamma R) or a control construct. Clones were isolated and tested for IFN-gamma stimulation of MHC I expression, sensitivity to IFN-gamma growth effects in vitro, and specific [125I]IFN-gamma binding.


RESULTS
The antisense strategy was successful in decreasing the number of cell-surface IFN-gamma binding sites and in vitro response to IFN-gamma. Finally, in vivo experiments demonstrated significantly increased untransfected tumor growth rate in animals after blockade of endogenous IFN-gamma by a single dose of anti-IFN-gamma antibody and more rapid growth of the IFN-gamma R-deficient cells compared to controls.


CONCLUSIONS
endogenous IFN-gamma has a direct effect on this less immunogenic tumor in vivo, which serves to slow growth and which is, at least partially, mediated through interferon-gamma receptors on the tumor cell.
Doherty
G M
GM
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA. doherty@wudos2.wustl.edu
Tsung
K
K
McCluskey
B
B
Norton
J A
JA
D000818:Animals; D000906:Antibodies / Q000276:immunology; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016375:Antisense Elements (Genetics); D015395:Histocompatibility Antigens Class I; D015335:Molecular Probes; D011956:Receptors, Cell Surface; D007371:Interferon-gamma