Natural killer cell as the effector which mediates in vivo apoptosis in AK-5 tumor cells.

AK-5 tumor cell death is mediated by natural killer cells through necrosis (perforin mediated) and apoptosis. Apoptosis is the mechanism which operates in immune animals in vivo. We have identified natural killer (NK) cell as the effector cell which induces apoptosis leading to tumor cell death in vivo. Naive NK cell which is unable to kill the AK-5 tumor cell can be activated with IL-2/IL-12 to make it capable of inducing apoptosis in tumor cells. NK cells from tumor-rejected animals show higher expression of Fas ligand and serine esterase granzyme B. In addition, NK cell-mediated apoptosis in AK-5 cells is totally abolished when effector cells are treated with anti-NKR-P1 mAb 3.2.3 and complement. NK cell-mediated apoptotic activity is inhibited in bcl-2 transfected tumor cells; however, the cytotoxic activity (perforin-mediated) remains unaffected. These observations suggest an important role for activated NK cells in inducing tumor cell death through necrosis (ADCC) and apoptosis leading to spontaneous regression of the AK-5 tumor in syngeneic animals.