Differential modulation by tumor necrosis factor and immune interferon of HLA class‐II antigens expressed by melanoma cells

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Abstract
Tumor necrosis factor (TNF‐α) was compared to immune interferon (IFN‐γ) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule I (ICAM I) 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‐γ and the cell lines SK‐MEL‐93‐DX‐2 and SK‐MEL‐93‐DX‐3, which originated from anatomically distinct metastases in patient DX. TNF‐α enhanced the expression of HLA class‐l antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN‐γ and the combination of IFN‐γ and TNF‐α. TNF‐α 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 IFN‐γ 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. Interestingly, both TNF‐α and IFN‐γ enhanced the expression of HLA class‐ll antigens by SK‐MEL‐93‐DX‐3 cells. On the other hand only TNF‐α induced the expression of HLA class‐ll antigens by MeWo cells and only IFN‐γ induced such expression by MeM 50–10 cells and by SK‐MEL‐93‐DX‐2 cells. The effect of the combination of TNF‐α and IFN‐γ was similar to that of the individual cytokines. Both TNF‐α and IFN‐γ 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 β‐, DQ β‐ and DP β‐specific probes suggests that the modulation of HLA class‐ll antigens by both cytokines reflects transcriptional and posttranscriptional events. TNF‐α enhanced the expression of ICAM‐I on all the melanoma cell lines, although to a lower extent than IFN‐γ and the combination of IFN‐γ and TNF‐α. Lastly, neither TNF‐α nor IFN‐γ displayed a marked effect on the expression of HMW‐MAA by the melanoma cell lines tested.

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