Antiblastic chemotherapy drugs up-modulate interferon-γ receptor expression on human malignant T cells

We have previously shown that the contrasting ability of interferon-γ (IFN-γ) either to stimulate the proliferation of malignant T cells or to induce their apoptosis is determined by the low and high intensity of IFN-γ receptor (IFN-γR) expression, respectively. High IFN-γR expression is a marker for the T cell stress that precedes 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 chemotherapy drugs (etoposide, cisplatin, cytarabin, and daunomycin) up-modulates their IFN-γR expression followed by their apoptosis after 24-48 h later. Increased IFN-γR expression (by at least an order of magnitude) was observed in 30 to 90% of cells during exposure to pharmacologic drug concentrations. Timely combination of chemotherapy drugs with IFN-γ may thus provide a more effective way of inhibiting the progress of human malignant T cells through synergistic induction of their apoptosis.