Resistance of Ha-ras oncogene-induced progressor tumor variants to tumor necrosis factor and interferon-γ

A. Fernandez, P. W. Chen, B. B. Aggarwal, H. N. Ananthaswamy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

To elucidate the mechanisms by which tumor cells escape the immune defenses of the normal host, we have isolated progressor tumor variants from a regressor tumor cell line by transfection with an activated Ha-ras oncogene. We previously found that the progressor phenotype of Ha-ras-induced variants was not due to loss of tumor-specific or major histocompatibility complex antigens. In this study, we investigated whether there is any correlation between in vivo tumor growth and in vitro sensitivity of regressor and progressor tumor cells to tumor necrosis factor (TNF). The regressor UV-2240 tumor cells, which do not grow in normal syngeneic mice, were sensitive to killing by TNF, whereas the Ha-ras oncogene-induced progressor tumor variants of UV-2240, which produce tumors in normal syngeneic hosts, were resistant to killing by TNF. Interferon-γ (IFN-γ) enhanced TNF-induced cytotoxicity of the regressor tumor cells, but it had no effect on Ha-ras-induced progressor tumor variants. The resistance of the Ha- ras-induced progressor variants to TNF and IFN-γ could be attributed to a decrease in the number of TNF receptors on their cell surface. However, there was no correlation between TNF and IFN-γ sensitivity of tumor cells and sensitivity to killing by activated macrophages, NK or NC cells. These results indicate that in some murine tumor cells, there may be a relationship between in vivo tumor growth and in vitro resistance to cytolysis by TNF and IFN-γ. Although the response of the Ha-ras-induced progressor variants to TNF and IFN-γ produced endogenously in immunocompetent mice is unknown, one can infer that some tumors escape the immune defenses of the normal host by becoming resistant to certain cytokines produced by the immune system.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalLymphokine and Cytokine Research
Volume11
Issue number2
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Hematology

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