title: Potentiation of interferon induction of class I major histocompatibility complex antigen expression by human tumor necrosis factor in small cell lung cancer cell lines.
abstract: The response of class I major histocompatibility complex antigen expression to in vitro administration of interferon and tumor necrosis factor alpha (TNF-alpha) was measured using class I major histocompatibility complex-deficient small cell lung cancer cell lines. Significant induction also was observed using gamma interferon (IFN-gamma) alone, whereas TNF-alpha alone yielded only modest induction. Classic small cell lung cancer cell lines NCI-H146 and NCI-H209 best demonstrated synergistic HLA and beta 2-microglobulin antigen induction with IFN-gamma and TNF-alpha with the following dose schedule: 3-6 days of TNF-alpha (200 units/ml) followed by 48 h of IFN-gamma (100 IU/ml). Induction was quantitated using an 125I-Protein A radioimmunoassay. Synergistic induction of the HLA and beta 2-microglobulin surface antigens on NCI-H146 was also possible with alpha interferon and TNF-alpha but required a higher concentration of the interferon, i.e., 3-6 days of TNF-alpha (200 units/ml) followed by 48 h of alpha interferon (1000 units/ml). Small cell lung cancer cell line NCI-H146 was further studied for expression of major histocompatibility complex messenger RNA using the optimal doses and sequence of addition of IFN-gamma and TNF-alpha as indicated above. A significant induction with IFN-gamma alone and synergistic induction with both IFN-gamma and TNF-alpha was quantitated for both HLA-A2 and beta 2-microglobulin transcripts using Northern blot analysis. Incubation with relatively low subcytotoxic doses of IFN-gamma and TNF-alpha also resulted in a marked synergistic decrease in c-myc message.
authors.affiliation: University of Maryland Cancer Center, Baltimore 21201.
authors.forename: G M
authors.initials: GM
authors.lastname: Marley
authors.forename: L A
authors.initials: LA
authors.lastname: Doyle
authors.forename: J V
authors.initials: JV
authors.lastname: Ordóñez
authors.forename: A
authors.initials: A
authors.lastname: Sisk
authors.forename: A
authors.initials: A
authors.lastname: Hussain
authors.forename: R W
authors.initials: RW
authors.lastname: Yen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma