Inhibition of natural killer activity by tumor-associated lymphoid cells from ascites ovarian carcinomas

Abstract

Tumor-associated lymphocytes (TAL) were isolated from ascites ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. TAL had low levels of natural killer (NK) activity compared to levels of peripheral blood lymphocytes (PBL) from the same patients or control subjects. When TAL were mixed with PBL, significant inhibition of NK activity was observed in 7 of 27 patients tested, with the suppression levels ranging from 14 to 60%. Inhibition of PBL NK activity was observed at the ratio of TAL to PBL of 1:1 or 2:1. Suppression of NK activity was detected with effector-to-target cell ratios ranging from 6:1 to 25:1 and at incubation time from 4 to 20 hours in the cytolysis assay. Tumor-associated macrophages from 6 patients were tested for suppression of NK activity. Only with 1 donor was a 17% inhibition observed at a ratio of macrophages of PBL of 1:1. Thus suppression by mature plastic adherent macrophages does not play a major role in the determination of the low levels of NK in human ascites ovarian tumors and the inhibitory activity of suppressor TAL, which had a minor contamination (less than 5%) with mononuclear phagocytes. When TAL from 1 patient with suppressive activity were passed through nylon wool, inhibition of NK activity was observed with both adherent and nonadherent cells.