Enhanced in vitro macrophage cytotoxicity against interferon-treated B16 melanoma cells.

Resistance to the in vitro antiproliferative effects of INF-alpha rapidly develops in mouse B16 melanoma cells that are maintained in vitro in IFN-alpha (B16 alpha res cells). B16 alpha res cells, however, are significantly more sensitive to the antitumor effects of IFN-alpha when they are injected into mice. This enhanced sensitivity appears to be due, at least in part, to activated macrophages. To investigate enhanced macrophage sensitivity of B16 alpha res cells, macrophage-mediated cytotoxicity assays have been performed using both B16 and B16 alpha res cell targets. Thioglycollate-elicited peritoneal macrophages activated in vitro with IFN-gamma exhibited dose-dependent cytotoxicity against both B16 and B16 alpha res cells, but significantly higher levels of cytotoxicity occurred with B16 alpha res targets. Kinetics experiment results showed that the cytolytic effects against B16 alpha res cells occurred at a very much faster rate than the cytolytic effects against B16 cells (50% cytotoxicity with 2 h of incubation versus 40% cytotoxicity by 24 h, respectively). Finally, peritoneal macrophages from B16-inoculated mice also were significantly more cytotoxic against B16 alpha res cells than against B16 cells. Macrophages from B16 alpha res-inoculated mice were significantly more cytotoxic against B16 alpha res cells than were macrophages from B16-inoculated mice. Taken together, these observations provide in vitro evidence to support the suggestion that peritoneal macrophages are important mediators of the enhanced host-mediated antitumor effects against B16 alpha res cells.