Augmentation of natural killer cell activity by biological response modifiers and significance of suppressor cells in the spleen of cancer patients

Spleen cells (SC) obtained from gastric and esophageal cancer patients were tested for natural killer (NK) cell activity against K 562 cells and non-specific suppressor cell activity against lymphocyte proliferative response to phytohemagglutinin, in comparison with those of splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL). Furthermore, in vitro effects of biological response modifiers (BRM), recombinant interleukin-2 (IL-2), human lymphoblast interferon (IFN) or a streptococcal preparation, OK-432, on the augmentation of NK cell activity were investigated in the presence of suppressor cells. In PBL obtained from cancer patients, NK cell activities tended to decline according to the advance of the disease, and positive suppressor cell activities were frequently detected in advanced cases. Similarly, positive suppressor cell activities were frequently detected in SVL and SC from advanced cancer patients, though high NK cell activities were observed in several advanced cancer patients with negative suppressor cell activities. NK cell activities of PBL in normal control donors were strongly augmented by IL-2, IFN or OK-432. Similarly, these agents exhibited the capacity to augment NK cell activities of PBL and SVL in cancer patients. On the other hand, NK cell activities of SC were similarly augmented by IL-2 or OK-432, not by IFN, in cancer patients. Moreover, NK cell activities of PBL, SVL or SC with negative suppressor cell activity were augmented by these BRMs in many cases. However, incidence of cases with significantly augmented NK cell activity by these agents in PBL, SVL or SC with positive suppressor cell activity tended to be lower than that with negative suppressor cell activity. These results suggested that NK cell activity might be regulated by non-specific suppressor cells, and the presence of suppressor cells might affect the augmentation of NK cell activity by BRM in circulating blood lymphocytes and also in spleen cells in cancer patients. IL-2 and OK-432 might be effective on the enhancement of immunological response in the presence of suppressor cells, but IFN might not.