Lymphotoxin enhances the susceptibility of neoplastic and preneoplastic cells to natural killer cell mediated destruction.

Treatment of neoplastic guinea-pig cells for 1-14 days with 300 units of guinea-pig lymphotoxin/ml medium enhanced 2- to 5-fold their susceptibility to natural killer (NK) cell-mediated cytotoxicity as measured by 4 h 51Cr and 72 h [3H]-thymidine-release assays. The NK susceptibility of human neoplastic and guinea-pig non-neoplastic cells refractory to guinea-pig lymphotoxin growth-inhibitory activity was unchanged after lymphotoxin treatment. Lymphotoxin preparations were free of detectable interferon and the enhancing activity copurified with lymphotoxin during diafiltration and isoelectric focusing. Treatment of NK cells with lymphotoxin preparations also augmented NK-mediated lysis but that activity did not copurify with lymphotoxin. As with neoplastic cells, lymphotoxin-sensitive preneoplastic cells previously treated with ultraviolet light, a chemical carcinogen, or carcinogen and the tumor-promoting agent tetradecanoylphorbol-acetate also exhibited lymphotoxin enhancement to NK-cell destruction. Thus, the immunologic hormone lymphotoxin enhances the susceptibility of lymphotoxin-sensitive cells to NK-cell destruction, indicating that these two natural immune mediators, lymphotoxin and NK cells, have the potential in concert to regulate carcinogenesis and neoplastic growth.