IMPAIRED NK RESPONSE OF CANCER-PATIENTS TO IFN-ALPHA BUT NOT TO IL-2 - CORRELATION WITH SERUM IMMUNOSUPPRESSIVE ACIDIC PROTEIN (IAP) AND ROLE OF SUPPRESSOR MACROPHAGE

In vitro NK responses of cancer patients (N=21) to rIFN-alphaA and rIL-2 were examined. The serum concentration of IAP (immunosuppressive acidic protein) was determined in parallel. Five out of seven patients whose serum IAP contents were within the normal range (270 mug/ml to 470 mug/ml), had their NK activities significantly augmented by rIFN-alphaA and rIL-2. On the other hand, NK cells from ten out of fifteen patients whose serum IAP concentrations were 650 mug/ml or more, were not activated by rIFN-alphaA. NK cells of these fifteen patients yet were capable of responding to rIL-2. NK cells from cancer patients, however, became responsive to rIFN-alphaA by either removal of adherent cells or treatment with indomethacin. Therefore, macrophages in PBMC of cancer patients with high serum IAP levels seem to selectively suppress NK response to rIFN-alphaA by an indomethacin-sensitive mechanisms. It was further shown that PGE2 was not the mediator of this suppression.