Fas-Fas ligand-based interactions between tumor cells and tumor-specific cytotoxic T lymphocytes: A lethal two-way street

In the current study, we investigated the repercussions of the interaction between tumor cells (LSA) and the tumor-specific cytotoxic T lymphocyte (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 cells used both perforin-and Fast-based pathways to kill Fas-positive (Fas(+)) LSA tumor cells. Interestingly, LSA tumor cells also constitutively 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 the presence of cell lysates of Fast-bearing LSA cells but not FasL-deficient P815 cells, exhibited significant apoptosis as detected using the TUNEL method. Moreover, another Fast(+) T-cell lymphoma line, EL-4, induced apoptosis in Fas(+) but not in Fas(-) T cells in a similar fashion. 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 accomplish this task more efficiently, The current study also suggests that Fast-based killing of CTLs by specific tumor cells may constitute a major limiting factor in successful immunotherapy. (C) 1997 by The American Society of Hematology.