The effect of interferon-gamma treatment of rat tumour cells on their susceptibility to natural killer cell, macrophage and cytotoxic T-cell killing.

Abstract

The effect of exposing tumour cells to interferon-gamma (IFN-gamma) has been studied investigating changes in MHC antigen expression and susceptibility to a variety of cellular effector mechanisms. Treatment of rat tumour cell lines with rat recombinant IFN-gamma increased their expression of class I MHC molecules, as monitored by quantitative immunofluorescence. Reduced sensitivity to lysis by NK cells was observed, although cold-target competition assays indicated NK cells were bound equally well by both interferon-treated and control cells. Decreased susceptibility to NK lysis was not a general effect of IFN-gamma treatment of tumour cells, as the sensitivity to lysis by activated macrophages was unaffected. Furthermore, both allogeneic CTL and CTL from syngeneic tumour-immune rats were able to kill IFN-gamma-treated tumour cells more effectively than untreated control target cells. These studies show that IFN changes the balance of sensitivity to different cytolytic effector mechanisms, increasing T-cell mediated effects, decreasing NK killing, but leaving macrophage cytotoxicity unaffected. The impact of these changes on tumour rejection will depend on the relative contribution of these mechanisms to target-cell destruction.