Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFNγ receptors

Anand S. Dighe, Elizabeth Richards, Lloyd J. Old, Robert D. Schreiber

Research output: Contribution to journalArticlepeer-review

467 Scopus citations

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.

Original languageEnglish
Pages (from-to)447-456
Number of pages10
JournalImmunity
Volume1
Issue number6
DOIs
StatePublished - Sep 1994

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