Lymphotoxin amplification of tumor growth inhibition is specific for natural killer cells but not for macrophages.

Lymphotoxin augments the susceptibility of tumorigenic guinea-pig cells to natural killer (NK) cell cytolysis in vitro but does not directly stimulate either NK cell or macrophage cytolytic action. The question whether lymphotoxin enhances the susceptibility of tumorigenic guinea-pig cells to cytolysis or other means of growth inhibition in vivo by syngeneic NK cells or macrophages was, therefore, examined using a modified tumor cell neutralization (Winn) assay. Mineral oil-, thioglycollate- or casein-induced peritoneal leukocytes, but not the macrophages isolated from the elicited leukocytes obtained from nonimmunized strain 2/N guinea-pigs, effected enhanced cytolysis of lymphotoxin-treated guinea-pig benzo (a)pyrene-induced 104CI tumor cells in vitro. Neither guinea-pig splenic NK cells nor oil-induced peritoneal macrophages alone inhibited the growth of 104CI cells as tumors in vivo when admixed with 104CI cells and injected into guinea-pigs. However, when the 104CI cells were treated with lymphotoxin before addition of effector cells, NK cells but not macrophages significantly reduced tumor growth in vivo. Therefore, the ability of lymphotoxin to increase the sensitivity of tumor cells to destruction mediated by natural leukocytes is specific for NK cells as compared to macrophages. This form of lymphokine amplification of natural leukocyte cytotoxicity may be one mechanism by which natural and acquired immunity serves or fails to prevent cancer and should be an important consideration in therapeutic approaches to eradicate or control tumor growth.