Interleukin-12 induces efficient lysis of natural killer-sensitive and natural killer-resistant human osteosarcoma cells: The synergistic effect of interleukin-2

Previously we demonstrated that some osteosarcoma cell lines varied greatly in their susceptibility to natural killer (NK) cell lysis in vitro. The ex pression of CD54 and CD58 adhesion molecules on their surface appeared to i nfluence their vulnerability, and the tumour necrosis factor-alpha (TNF-alp ha)-induced positive modulation of CD54 increased osteosarcoma susceptibili ty in vitro. This study investigated whether peripheral blood mononuclear c ells from normal healthy donors could be activated by interleukin (IL)-12 a nd IL-2, separately or in combination, to lyse osteosarcoma cell lines in v itro, as evaluated by using a microcytotoxicity test. In addition, we analy sed (by flow cytometry) whether this function correlated with modifications of the CD2, CD11a, CD11b and CD18 molecules, which are involved in the adh esion of effector cells to the counter-receptors (CD54 and CD58) on osteosa rcomas. This study demonstrates that incubation with IL-12 and/or IL-2 trig gered NK cell cytolytic activity against osteosarcoma targets and that cyto lytic activity was enhanced to a greater extent when lymphocytes were incub ated simultaneously with a combination of IL-12 and IL-2. The density of CD 18 and CD2 molecules involved in NK adhesion was also up-modulated followin g cytokine incubation. These changes in the density of adhesion molecules c an be involved in the increased lytic activity of effector lymphocytes and in the modification of their binding capacity to osteosarcoma target cells.