Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFNγ receptors
- 1 September 1994
- journal article
- research article
- Published by Elsevier BV in Immunity
- Vol. 1 (6), 447-456
- https://doi.org/10.1016/1074-7613(94)90087-6
Abstract
Using a neutralizing monoclonal antibody specific for murine IFNy we show that endogenously produced IFNγ plays an obligate role in mediating LPS-induced rejection of the Meth A fibrosarcoma tumor in syngeneic BALE/c mice. To examine the cellular targets of IFNγ action, we generated IFNγ-insensitive tumor cells by stably overexpressing in Meth A a truncated dominant negative form of the murine IFNγ receptor a chain. When implanted in BALB/c mice, IFNγ-insensitive Meth A cells displayed enhanced tumorigenicity compared with control Meth A cells and were not rejected when tumor-bearing mice were treated with concentrations of LPS that eliminated control tumors. In Meth A immune mice, IFNγ-sensitive Meth A did not establish tumors while IFNγ-insensitive tumors grew in a progressive manner. In addition, the IFNγ-insensitive tumor cells were unable to elicit strong protective immunity to subsequent wild-type tumor challenge. These results show that IFNγ has direct effects on tumor cell immunogenicity and thus plays an important role in promoting tumor cell recognition and elimination.Keywords
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