Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors

Lymphocytes and tumor cells were isolated from the carcinomatous ascites of 24 patients with epithelial ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll-Isopaque gradients and fetal bovine serum. Tumor-associated lymphocytes showed a lower percentage of cells with receptors for sheep erythrocytes (E) or for complement than did peripheral blood lymphocytes from the same patients. NK activity was measured, 51Cr-labelled K562 cells being used as targets in a 20-h assay. Tumor-associated lymphocytes showed significant NK activity. Cytotoxicity levels were lower than for peripheral blood effector cells from the same patients, and these in turn showed significantly lower cytotoxic capacity than peripheral blood lymphocytes from 64 control subjects. Similar results were obtained when lysis was measured after 4 h of incubation. Tumor-associated lymphocytes forming E rosettes were at least as effective as the unseparated population. When tumor-associated lymphocytes were mixed with normal effector cells, in three of six preparations with low NK activity tested, significant inhibition of normal lymphocyte NK activity was observed. Adherent macrophages from carcinomatous ascites, which contained lymphocytes that had suppressive activity, showed no inhibitory activity. Interferon (IF) boosted the NK activity against K562 of tumor-associated lymphocytes. Purified ovarian carcinoma cells were relatively resistant to lysis by normal lymphocytes. However, they inhibited lysis of K562 cells in cold target competition assays, though less efficiently than K 562 itself, and were consistently lysed when effector cells were stimulated with IF. It is therefore suggested that ovarian carcinoma cells express NK-relevant recognition structures, but are relatively resistant to cytolysis by unstimulated effector cells.