ANTIBLASTIC CHEMOTHERAPY DRUGS UP-MODULATE INTERFERON-GAMMA RECEPTOR EXPRESSION ON HUMAN-MALIGNANT T-CELLS

We have previously shown that the contrasting ability of interferon-ga mma (IFN-gamma) either to stimulate the proliferation of malignant T c ells or to induce their apoptosis is determined by the low and high in tensity of IFN-gamma receptor (IFN-gamma R) expression, respectively. High IFN-gamma R expression is a marker for the T cell stress that pre cedes apoptosis. In this paper, we show that a 12- to 24-h culture of three human malignant T-cell lines displaying distinct differentiation stages (ST4, PF382, and Jurkat) in medium supplemented with four chem otherapy drugs (etoposide, cisplatin, cytarabin, and daunomycin) up-mo dulates their IFN-gamma R expression followed by their apoptosis after 24-48 h later. Increased IFN-gamma R expression (by at least an order of magnitude) was observed in 30 to 90% of cells during exposure to p harmacologic drug concentrations. Timely combination of chemotherapy d rugs with IFN-gamma may thus provide a more effective way of inhibitin g the progress of human malignant T cells through synergistic inductio n of their apoptosis.