Tumor necrosis factor-alpha and interferon-gamma induce expression of functional Fas ligand on HT29 and MCF7 adenocarcinoma cells

Tumor cells develop diverse mechanisms to escape from immune surveillance, including expression of Fas ligand (Fast), a 40-kDa type II transmembrane p rotein that mediates apoptosis by binding to its cognate receptor Fas (APO- 1/CD95). Upon activation, T lymphocytes and natural killer (NK) cells expre ss Fas and thus become sensitive to Fast-mediated apoptosis. Here we show t hat tumor necrosis factor-alpha (TNF-alpha) in addition to interferon-gamma (IFN-gamma) induces cell surface expression of functional Fast in human HT 29 colon and MCF7 breast adenocarcinoma cells that constitutively lack cell surface expression of Fast. These cells, expressing Fast, are capable of i nducing apoptosis in Fas-positive Jurkat T cells mediated by plasma membran e-bound Fast and soluble forms of Fast, By contrast, mutational deletion of Fas cell surface expression as web as inhibition of caspase family proteas es involved in Fas signaling and monoclonal antibodies neutralizing Fast pr otect Jurkat T cells from apoptosis caused by the Fast-expressing HT29 or M CF7 cells. These results demonstrate that TNF-alpha and IFN-gamma induce ex pression of functional Fast in adenocarcinoma cells which thereby can kill T lymphocytes by the FasL/Fas pathway. (C) 1999 Academic Press.