ENHANCED EXPRESSION OF HLA-A,B,C AND INDUCIBILITY OF TAP-1, TAP-2, AND HLA-A,B,C BY INTERFERON-GAMMA IN A MULTIDRUG-RESISTANT SMALL-CELL LUNG-CANCER LINE

Recent evidence suggests that deficient HLA Class I expression in SCLC lines may be due, in part, to down-regulation of TAP-1 and TAP-2 expr ession, and, thus, deficient antigen processing. Given the capability of the multidrug transporter mediating MDR, P-gp, to transport peptide s, we hypothesized that P-gp may substitute for TAP-1/TAP-2 and enhanc e antigen processing in SCLC. To investigate this, we studied the H69 line (parent SCLC) and VPR-2 (MDR subline selected in etoposide, P-gp +). HLA-A,B,C expression was significantly increased in VPR-2 cells re lative to H69, and was much more inducible with IFN-gamma. TAP-1 and T AP-2 were expressed at low levels in both lines. Differential inductio n of TAP-1 expression with IFN-gamma exposure was observed, with a dra matic increase in VPR-2 cells, and no change in H69. TAP-2 expression was enhanced in both lines with IFN-gamma, but to a greater degree in VPR-2. VPR-2 cells were resistant to LAK killing relative to H69, and were minimally sensitized with IFN-gamma. In contrast, IFN-gamma enhan ced susceptibility of H69 to LAK killing 3-fold. The direct correlatio n between enhancement of HLA-A,B,C expression by IFN-gamma and the dif ferential inducibility of TAP-1 and TAP-2 expression in P-gp-SCLC line s is novel. Relative LAK sensitivity of H69 and its increase by IFN-ga mma may have clinical implications.