FAS-FAS LIGAND-BASED INTERACTIONS BETWEEN TUMOR-CELLS AND TUMOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTES - A LETHAL 2-WAY STREET

In the current study, we investigated the repercussions of the interac tion between tumor cells (LSA) and the tumor-specific cytotoxic T lymp hocyte (CTL) (PE-9) when both expressed Fas and Fas ligand (Fast). The CTL clone, PE9, expressed high levels of Fas and Fast upon activation through the T-cell receptor (TCR). Furthermore, the activated PE-9 ce lls used both perforin-and Fast-based pathways to kill Fas-positive (F as(+)) LSA tumor cells. Interestingly, LSA tumor cells also constituti vely expressed Fast but not perforin, and killed Fas(+) PE-9 CTLs and Fas(+) but not Fas-negative (Fas(-)) activated T cells and thymocytes, as detected using the JAM test. PE-9 CTLs, cultured for 24 hours in t he presence of cell lysates of Fast-bearing LSA cells but not FasL-def icient P815 cells, exhibited significant apoptosis as detected using t he TUNEL method. Moreover, another Fast(+) T-cell lymphoma line, EL-4, induced apoptosis in Fas(+) but not in Fas(-) T cells in a similar fa shion. The current study demonstrates for the first time that not only can the tumor-specific CTL mediate Fas-based killing of tumor cells, but FasL(+) tumor cells can kill the Fas(+) tumor-specific CTL. Thus, the survival of the tumor or the host may depend on which cell can acc omplish this task more efficiently, The current study also suggests th at Fast-based killing of CTLs by specific tumor cells may constitute a major limiting factor in successful immunotherapy. (C) 1997 by The Am erican Society of Hematology.