Effect of tumor necrosis factor and interferon gamma on human renal carcinoma cell line growth

Four human renal carcinoma cell lines (786-0, CaKi-1, TK-10 and TK-164) were studied in vitro for susceptibility to human recombinant interferon-gamma (IFN gamma) and/or human recombinant tumor necrosis factor (TNF). All four cell lines tested demonstrated a dose dependent sensitivity to the cytotoxic effects of TNF alone. The degree of sensitivity varied for each cell line. IFN gamma alone also mediated a dose dependent antiproliferative effect in three of the four cell lines. Combinations of IFN gamma and TNF produced diverse inhibitory effects. Preincubation of the cells for various time intervals with noninhibitory concentrations of IFN gamma prior to the addition of TNF resulted in distinct effects for each cell line. Pretreatment enhanced the cytotoxic effect of TNF for some cell lines; however, others became less susceptible and some demonstrated enhanced proliferation in the presence of both agents. Optimal pretreament times also varied from cell line to cell line. These results demonstrate variability in responsiveness by renal carcinoma cell lines to combination IFN gamma and TNF treatments and suggest that timing as well as concentration may be important in in vivo therapy.