Defective interferon-augmented natural killer cell activity in patients with metastatic malignant melanoma

Unstimulated and interferon (IFN)-stimulated natural killer cell (NK) activity was investigated in patients with malignant melanoma prior to the removal of the primary melanoma (stage I disease) or in patients with melanoma metastases. Unstimulated as well as IFN-stimulated NK activities, directed against the primarily NK-sensitive K562 cell line, were found not to differ significantly from the NK activity of healthy control subjects. In contrast, IFN-stimulated NK activity directed against the primarily NK-insensitive Chang hepatoma and JY cell lines was significantly lower in patients with metastatic melanoma than in patients with non-metastatic disease (Chang hepatoma cell line: P less than 0.02; JY cell line: P less than 0.0017) and - in experiments using the JY cell line - than in healthy controls (P less than 0.01). Stage I melanoma patients did not differ in their IFN-induced NK activity from healthy control subjects using Chang hepatoma and JY cell lines. Finally, the IFN-induced increase in NK activity directed against primarily NK-insensitive target cell lines was significant in stage I melanoma patients and in healthy controls (P less than 0.01, respectively), but not in patients with metastatic melanoma (P greater than 0.5). We thus conclude that patients with metastatic malignant melanoma exhibited a defect in IFN-augmented NK activity directed against primarily NK-insensitive targets.