Modulation of natural killing by tumor promoters: the regulatory influence of adherent cells varies with the type of target cell.

We have analyzed the regulatory effects of two classes of tumor promoters, phorbol diesters and indole alkaloids, on human natural killer (NK) cell activity in vitro. In accordance with previous reports, we found that 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited natural killing against K 562 targets by unseparated mononuclear cells. Here, suppression of NK required the presence of adherent cells (macrophages). Contrary to the results obtained with K 562, tumor promoter-induced suppression of NK activity tested against U 937, another cell line of known NK susceptibility, was independent of the presence of adherent cells. Thus, NK cytotoxicity of effector cells rigorously depleted of adherent and Ia-positive cells was still inhibited when assayed against U 937, while it was generally enhanced when tested against K 562. Identical results were obtained with teleocidin and dihydroteleocidin B, two members of the recently discovered indole alkaloid class of tumor promoters. Therefore, we demonstrate that the regulatory effect of tumor promoters on human NK activity (suppression or stimulation) is determined not only by macrophages at the effector cell level but also by the type of target cell under study.