Tumor necrosis factor-α and interferon-γ 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 protein that mediates apoptosis by binding to its cognate receptor Fas (APO-1/CD95). Upon activation, T lymphocytes and natural killer (NK) cells express Fas and thus become sensitive to Fast-mediated apoptosis. Here we show that tumor necrosis factor-alpha (TNF-alpha) in addition to interferon-gamma (IFN-gamma) induces cell surface expression of functional Fast in human HT29 colon and MCF7 breast adenocarcinoma cells that constitutively lack cell surface expression of Fast. These cells, expressing Fast, are capable of inducing apoptosis in Fas-positive Jurkat T cells mediated by plasma membrane-bound Fast and soluble forms of Fast, By contrast, mutational deletion of Fas cell surface expression as web as inhibition of caspase family proteases involved in Fas signaling and monoclonal antibodies neutralizing Fast protect Jurkat T cells from apoptosis caused by the Fast-expressing HT29 or MCF7 cells. These results demonstrate that TNF-alpha and IFN-gamma induce expression of functional Fast in adenocarcinoma cells which thereby can kill T lymphocytes by the FasL/Fas pathway. (C) 1999 Academic Press.