title: Differential modulation by tumor necrosis factor and immune interferon of HLA class-II antigens expressed by melanoma cells.
abstract: Tumor necrosis factor (TNF-alpha) was compared to immune interferon (IFN-gamma) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule I (ICAM I) and of high-molecular-weight melanoma-associated 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-II antigens by IFN-gamma 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-alpha enhanced the expression of HLA class-I antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. TNF-alpha displayed a differential effect on the expression of HLA class-II antigens by the 7 melanoma cell lines: it enhanced it on 3 out of the 4 cell lines with constitutive expression of HLA class-II antigens and induced them on 1 of 3 cell lines without detectable expression of these antigens. The effects of IFN-gamma were different since it enhanced HLA class-II 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-alpha and IFN-gamma enhanced the expression of HLA class-II antigens by SK-MEL-93-DX-3 cells. On the other hand only TNF-alpha induced the expression of HLA class-II antigens by MeWo cells and only IFN-gamma induced such expression by MeM 50-10 cells and by SK-MEL-93-DX-2 cells. The effect of the combination of TNF-alpha and IFN-gamma was similar to that of the individual cytokines. Both TNF-alpha and IFN-gamma 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 beta-, DQ beta- and DP beta-specific probes suggests that the modulation of HLA class-II antigens by both cytokines reflects transcriptional and post-transcriptional events. TNF-alpha enhanced the expression of ICAM-I on all the melanoma cell lines, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. Lastly, neither TNF-alpha nor IFN-gamma displayed a marked effect on the expression of HMW-MAA by the melanoma cell lines tested.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
authors.forename: M
authors.initials: M
authors.lastname: Maio
authors.forename: B
authors.initials: B
authors.lastname: Gulwani
authors.forename: A
authors.initials: A
authors.lastname: Morgano
authors.forename: S
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D000954:Antigens, Surface / Q000032:analysis; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma