DRUG-RESISTANCE RESULTS IN ALTERATIONS IN EXPRESSION OF IMMUNE RECOGNITION MOLECULES AND FAILURE TO EXPRESS FAS (CD95)

It is demonstrated that methotrexate/cisplatin-sensitive L1210 cells e xpress low levels of major histocompatibility complex (MHC) class II r elative to the high levels expressed on methotrexate (MTX)/cisplatin-r esistant L1210/DDP cells. L1210 cells express cell-surface Fas, while the L1210/DDP cells express no cell-surface Fas. Expression of costimu latory molecules B7-1/B7-2 and Fas is increased on L1210 cells, but no t L1210/DDP, in the presence of methotrexate or trimetrexate (TMTX). T herefore, a component of the mechanism of action of some anti-cancer a gents may be to facilitate immune recognition and T cell-directed, Fas -induced cell death. Loss of cell-surface Fas expression and failure o f Fas (CD95)-dependent apoptotic death has been observed when cells de velop 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.