Effector function of lymphokine-activated killer cells and cytotoxic T lymphocytes in ovarian epithelial carcinoma

Abstract

From 20 patients with ovarian carcinoma (4 with stage I and 16 with stage III disease), we obtained peripheral blood mononuclear cells (MNC) from each, tumor-associated MNC from 9, and ascitic MNC from 6. These cells were stimulated with interleukin 2 (IL-2), and radioactive chromium-release cytotoxicity assays were used to evaluate the lymphokine-activated killer (LAK) activity against autologous tumor cells and two natural killer-resistant cell lines. The LAK response was consistently better with control peripheral blood MNC than with patient-derived MNC against all targets. However, within the ascitic MNC population, LAK activity against two cell lines (Daudi and OVCAR) was not statistically different from that of the control MNC. Phenotypic analysis of the ascitic MNC with monoclonal antibodies and flow cytometry revealed an activated population (IL-2 receptor-positive) characterized by predominantly monocytes/macrophages and T cells. In addition, the peripheral blood LAK activity for patients with stage I disease was statistically better against each target than that from patients with stage III disease. These results suggest an immunosuppressive effect directly related to tumor burden. Except perhaps for the ascitic MNC, autologous MNC do not appear to be effective LAK sources. Follow-up of the stage III patients revealed no difference in 2-year survival associated with in vitro LAK response.