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

Immunity. 1994 Sep;1(6):447-56. doi: 10.1016/1074-7613(94)90087-6.

Abstract

Using a neutralizing monoclonal antibody specific for murine IFN gamma we show that endogenously produced IFN gamma plays an obligate role in mediating LPS-induced rejection of the Meth A fibrosarcoma tumor in syngeneic BALB/c mice. To examine the cellular targets of IFN gamma action, we generated IFN gamma-insensitive tumor cells by stably overexpressing in Meth A a truncated dominant negative form of the murine IFN gamma receptor alpha chain. When implanted in BALB/c mice, IFN gamma-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, IFN gamma-insensitive Meth A did not establish tumors while IFN gamma-insensitive tumors grew in a progressive manner. In addition, the IFN gamma-insensitive tumor cells were unable to elicit strong protective immunity to subsequent wild-type tumor challenge. These results show that IFN gamma has direct effects on tumor cell immunogenicity and thus plays an important role in promoting tumor cell recognition and elimination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Interferon-alpha / immunology
  • Interferon-gamma / immunology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Neoplasm Transplantation / immunology
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology*
  • Receptors, Interferon / immunology*
  • T-Lymphocytes / immunology
  • Transfection / immunology
  • Tumor Cells, Cultured

Substances

  • Interferon-alpha
  • Lipopolysaccharides
  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma