Interferon Effect on Cytotoxicity of Peripheral Blood and Tumor-Associated Lymphocytes Against Human Ovarian Carcinoma Cells23

Abstract

A study was done to investigate the tumoricidal activity of peripheral blood lymphocytes (PBL) and tumor-associated lymphoid cells (TAL) against freshly isolated tumor cells in human ovarian carcinoma. TAL and carcinoma cells were purified by density and velocity sedimentation on discontinuous Ficoll-Hypaque gradients and fetal bovine serum. Purified carcinoma cells from 23 ascitic and 3 solid tumors were used as targets in a 4- or a 20-hour 51Cr release assay. K562 cells were used to measure natural killer (NK) activity. Freshly purified ovarian carcinoma cells were relatively resistant to lysis by normal unstimulated PBL. Cytolytic activity of ovarian cancer PBL and TAL did not exceed that of control PBL: Only one PBL preparation had high levels of cytotoxicity (36.2 and 42.9% specific lysis after 4 and 20 hr at an effector-to-target cell ratio of 50:1) against autologous cancer cells but not against allogeneic targets (less than 5% specific lysis). TAL and, to a lesser extent, ovarian cancer PBL showed impaired NK activity against K562 compared to the activity seen in controls. In vitro exposure to partially purified human fibroblast interferon (IFN) (1,000 U/ml for 1-18 hr) augmented NK activity against K562 of PBL and TAL. When ovarian carcinoma cells were used as targets, IFN enhanced the cytotoxicity of normal PBL in a 4- and 20-hour assay; stimulation by IFN was less frequently observed with ovarian cancer PBL and TAL in a 4-hour assay, but after 20 hours effector cells from tumor-bearing subjects showed IFN-boosted cytotoxicity against carcinoma cells similar to the degree of cytotoxicity seen in controls. IFN enhanced the cytotoxicity of PBL and TAL against both autologous and allogeneic carcinoma cells. Thus PBL and TAL are rarely cytotoxic against 51Cr-labeled fresh autologous carcinoma cells, but in vitro exposure to IFN induced low levels of killing of ovarian tumor cells.