Immune regulation of the L5178Y murine tumor-dormant state: induction of cell- and soluble factor-mediated inhibition of tumor cell growth by tumor necrosis factor and gamma-interferon.

Small concentrations of recombinant murine tumor necrosis factor (rMuTNF) synergized with recombinant murine gamma-interferon (rMuIFN-gamma) to inhibit tumor cell growth in peritoneal cell (PC) cultures from tumor-dormant mice. A soluble inhibitor of tumor cell growth was produced in the rMuTNF-treated PC cultures, but there was no synergistic enhancement of production of this inhibitor by the addition of rMuIFN-gamma. Treatment of both plastic-adherent PC and nonadherent PC cultures which contained L5178Y cells with rMuTNF + rMuIFN-gamma resulted in inhibition of tumor cell growth. However, in the absence of L5178Y cells, rMuTNF + rMuIFN-gamma induced antitumor cytotoxic activity in the plastic-adherent but not in the plastic nonadherent PC. These results indicate that the antitumor activity of rMuTNF + rMuIFN-gamma in PC from tumor-dormant mice involves both cell- and soluble factor-mediated mechanisms.