Melphalan and other anticancer modalities up-regulate B7-1 gene expressionin tumor cells

In this study, we show that administration of low-dose melphalan (L-PAM, L- phenylalanine mustard) to mice bearing a large MOPC-315 plasmacytoma led to a rapid up-regulation of B7-1 (CD80), but not B7-2 (CD86), expression on t he surface of MOPC-315 tumor cells. This L-PAM-induced preferential up-regu lation of B7-1 surface expression was due, at least in part, to a direct ef fect of L-PAM on the tumor cells, as in vitro exposure of MOPC-315 tumor ce lls to L-PAM led to the preferential up-regulation of B7-1 surface expressi on. Moreover, in vitro exposure of MOPC-315 tumor cells to two other antica ncer modalities, gamma-irradiation and mitomycin C, resulted in the prefere ntial up-regulation of B7-1 surface expression. This effect was not restric ted to MOPC-315 tumor cells, as preferential up-regulation of B7-1 surface expression was observed also following in vitro exposure of the P815 mastoc ytoma (that is negative for both B7-1 and B7-2 surface expression) to any o f the three anticancer modalities. The up-regulation of B7-1 surface expres sion following in vitro exposure of tumor cells to L-PAM, gamma-irradiation , or mitomycin C required de novo protein and RNA synthesis, and was associ ated with the accumulation of mRNA for B7-1 within 4-8 h, indicating that t he regulation of B7-1 expression is at the RNA transcriptional level. These results have important implications for an additional immune-potentiating mechanism of these anticancer modalities in clinical setting.