Published in Cancer Detection and Prevention 1997; 21(2):191-195.

Antiblastic Chemotherapy Drugs Up-Modulate Interferon-Y Receptor Expression on Human Malignant T Cells

F. Novelli, PhD, A. Allione, PhD, P. Bernabel, PhD, L. Higamonti, PhD, and G. Forni, MD

CNR-Center for Immunogenetics and Experimental Oncology, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

Address all correspondence and reprint requests to: Francesco Novelli, Ph.D., Dipartimento Scienze Cliniche e Biologiche, Universita' di Torino, Ospedale S. Luigi Gonzaga, 10043 Orbassano, Torino, Italy.

ABSTRACT: We have previously shown that the contrasting ability of interferon-gamma (IFN-gamma) either to stimulate the proliferation of malignant T cells or to induce their apoptosis is determined by the low and high intensity of IFN-gamma receptor (IFN-gammaR) expression, respectively. High IFN-gammaR 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-gammaR expression followed by their apoptosis after 24-48 h later. Increased IFN-gammaR 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-gamma may thus provide a more effective way of inhibiting the progress of human malignant T cells through synergistic induction of their apoptosis.

KEY WORDS: interferon-gamma receptor, malignant T cells, apoptosis.