Interferon-β Increases the Sensitivity of Endometrial Cancer Cells to Cell-Mediated Cytotoxicity

Abstract

Established monolayer cell lines derived from human endometrial carcinoma (Ishikawa and HEC-50) were sensitive to the cytotoxic activity of peripheral blood lymphocytes (PBLs). The percentages of hormone-responsive Ishikawa cells lysed by the cytotoxic activity of lymphocytes were 45.7 ± 4.3 (mean ± SE), 31.5 plusmn; 4.1, and 20.1 ± 1.6, at effector/target (E/T) ratios of 50:1, 25:1, and 12:1, respectively. Values of 44.7 ± 5.4%, 29.4 ± 4.6%, and 20 ± 4.9% were obtained when non-hormone-responsive HEC-50 cells were used as targets at the same E/T ratio. The percentages of epithelial and stromal cells, isolated from human endometrial cancer, lysed by the cytotoxic activity of lymphocytes were 40 ± 5.4 and 23.2 ± 3.8, respectively, at an E/T ratio of 25:1. The addition of interferon-β (IFN-β) to the culture increased tumor target cell sensitivity to the lytic activity of untreated PBL. The increase produced by 10 [U/ml of IFN-β ranged between 0.60- and 0.89-fold (P < 0.01 Student's t test, two-tailed, unpaired) in Ishikawa cells and between 0.37- and 0.72-fold P < 0.05) in HEC-50 cells. Higher concentrations of IFN-β (100 and 1000 IU/ml) were less effective in increasing the sensitivity of the target cells. There was no significant increase in the cytotoxic activity of lymphocytes treated with IFN-β whereas cytotoxic activity toward untreated tumor target cells increased when lymphocytes were treated with IFN-α. The effects of IFN-β were also evaluated using epithelial and stromal cells derived from human endometrial cancer. It was found that IFN-β at low concentrations (10 IU/ml) significantly increased the sensitivity of both epithelial and stromal cells, by 48 and 73%, respectively. Our data indicate that Ishikawa, HEC-50, epithelial, and stromal cells may provide a useful experimental model for studying the effects of immunomodulant agents such as IFN-β in hormone-related tumors. IFN-β increases endometrial target cell sensitivity, rather than the lytic activity of lymphocytes.