Tumor necrosis factor (TNF-a) was compared to immune interferon (IFNq) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule l (ICAM l) and of high-molecular-weight melanomaassociated antigen (HMW MAA) by a panel of melanoma cell lines. The latter included the melanoma cell line MeWo and its metastatic variant MeM 50-10, which display differential susceptibility to modulation of HLA class-ll antigens by IFN-y and the cell lines SK-MEL-93-DX-2 and SK-MEL-93-DX-3, which originated from anatomically distinct me-in patient DX. TNF-a enhanced the expression of HLA class4 antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN-y and the combination of IFN-y and TNF-a. T N F a displayed a differential effect on the expression of HLA class-ll antigens by the 7 melanoma cell lines: it enhanced it on 3 out of the 4 cell lines with constitutive expression of HLA class-ll antigens and induced them on I of 3 cell lines without detectable expression of these antigens. The effects of I F N y were different since it enhanced HLA class-ll antigens on the 4 cell lines with constitutive expression of these antigens and induced them on 2 out of the remaining 3 lines. lnterestin ly, both T N F a and IFN-y enhanced the expression of HJ class-ll antigens by SK-MEL-93-DX-3 cells.
On the other hand only T N F a induced the expression of HLA class-11 antigens by MeWo cells and only IFN-y induced such expression by MeM 50-10 cells and by SK-MEL93-DX-2 cells. The effect of the combination of T N F a and IFN-y was similar to that of the individual cytokines. Both TNF-a and IFN-y displayed a differential effect on the expression of the gene products of the HLA-D region by the melanoma cell lines.
Northern blot analysis with HLA-DR f3-, DQ f3and DP f3-specific probes suggests that the modulation of HLA class-ll antigens by both cytokines reflects transcriptional and posttranscriptional events. TNF-a enhanced the expression of ICAM-I on all the melanoma cell lines, although to a lower extent than 1FN-y and the combination of IFN-y and TNF-a. Lastly, neither T N F a nor IFN-y displayed a marked effect on the expression of HMW-MAA by the melanoma cell lines tested.