SENSITIZATION OF AIDS-RELATED NON-HODGKINS B-LYMPHOMA CELL-LINES TO CYTOTOXIC DRUGS TOXINS BY INTERFERON-GAMMA

AIDS-related lymphomas (ARL) progressively become resistant to convent ional chemotherapy. We have developed three B cell lines from tumor bi opsies of AIDS patients with non-Hodgkin's lymphoma (NHL). The ARL cel l lines were shown to be resistant to a panel of cytotoxic cytokines, toxins and drugs such as tumor necrosis factor, diphteria toxin, ricin , adriamycin, cis-platinum and anti-Fas antibody. However, when these cell lines were pretreated with low concentrations of interferon-gamma (IFN-gamma), (50 U/ml or 150 U/ml) for 24 to 48 h, the tumor cells be came sensitive to these cytotoxic agents. Pretreatment of ARL with IFN -gamma stimulated proliferation while IFN-gamma inhibited the growth o f ovarian tumor cell lines. Further, following treatment with IFN-gamm a, the secretion of TNF-alpha by ARL lines was significantly decreased and TNF-alpha surface receptor expression was downregulated. The expr ession of several surface antigens on ARL was upregulated by IFN-gamma . These findings demonstrate that treatment of ARL with IFN-gamma stim ulated cell proliferation, modulated several surface antigens, inhibit ed TNF-alpha secretion and sensitized the tumor cells to cytotoxicity by various drugs/toxins. These findings may be clinically relevant in the treatment of drug-refractory ARL.