Abstract
It is demonstrated that methotrexate/cisplatin‐sensitive L1210 cells express low levels of major histocompatibility complex (MHC) class II relative to the high levels expressed on methotrexate (MTX)/cisplatin‐resistant L1210/DDP cells. L1210 cells express cell‐surface Fas, while the L1210/DDP cells express no cell‐surface Fas. Expression of costimulatory molecules B7‐1/B7‐2 and Fas is increased on L1210 cells, but not L1210/DDP, in the presence of methotrexate or trimetrexate (TMTX). Therefore, a component of the mechanism of action of some anti‐cancer agents may be to facilitate immune recognition and T cell‐directed, Fas‐induced cell death. Loss of cell‐surface Fas expression and failure of Fas (CD95)‐dependent apoptotic death has been observed when cells develop drug resistance. The defect in apoptosis can be overcome by anti‐cancer agents or experimental manipulation that induce Fas expression on the drug‐resistant cells.