DEPLETION OF THE NATURAL-KILLER-CELL POPULATION IN THE PERITONEUM BY AK-5 TUMOR-CELLS OVEREXPRESSING FAS-LIGAND - A MECHANISM OF IMMUNE EVASION

AK-5 tumor hills 100% hosts when injected ip and only 20-30% of animal s die when the tumor cells are transplanted sc. Seventy percent of ani mals regress the subcutaneous tumor and exhibit total immunity against subsequent challenges of AK-5 cells by either route. Initially the 10 0% killing in ip-injected animals was attributed to the rapid growth o f the tumor cells in the peritoneum thereby not giving enough time for the host immune system to mount an antitumor response. In the present report we have demonstrated overexpression of Fas-L by day 3 and day 4 ascitic tumor cells which depletes the peritoneum of Fas(+) lymphocy tes. In addition the effector cells from the ascites are ineffective i n inducing cytotoxicity against tumor cells in vitro. However, splenoc ytes from animals bearing ip tumors possessed cytotoxicity against YAC -I as web as AK-5 cells. We have also shown the presence of soluble Fa s-L in the ascitic fluid, which induced DNA fragmentation in Fas(+) Ju rkat cells. Fas-L present in the tumor cells is able to induce apoptos is in activated lymphocytes and Jurkat cells, suggesting retention of its biological function. These studies implicate Fas-L in the depletio n of the effector cell number and inhibition of their functional activ ity. They also suggest differential regulation of Fas-L expression by the tumor cells depending upon the site of transplantation. (C) 1998 A cademic Press.