Tumor surveillance: expression of the transporter associated with antigen processing (TAP-1) in ex-vivo human tumor samples and its elevation by in vitro treatment with IFN-gamma and TNF-alpha.
We have analyzed 30 human tumor specimens (two breast, six lung, and 21 ovarian carcinomas and one malignant melanoma) for the expression of the transporter associated with antigen processing, TAP-1. Cell suspensions judged to contain negligible contamination with non-tumor cells were tested for reactivity with the antibody directed to TAP-1 in Western blot. According to these results all lysates prepared from the tumor samples contained the protein, but with considerable quantitative variations. Tumors exposed in vitro for a short time to IFN-gamma and TNF-alpha had elevated TAP-1 levels in 12 out of 30 experiments. In accordance with previous results, the tumor cell populations were heterogeneous with regard to MHC class I expression, as analyzed by indirect immunofluorescence on viable cell suspensions. Short term in vitro treatment with IFN-gamma and TNF-alpha elevated MHC class I expression in several tumors. In several mixed cultures, cytokine treated tumor cells induced cytotoxic activity in autologous or allogeneic lymphocyte populations. In vitro treatment with IFN-gamma and TNF-alpha upregulated thus the expression of MHC class I and TAP-1 in a fraction of the tumor samples. However the potentiation of the capacity to interact with T cells induced by the cytokines was not always parallel with the changes in these two parameters. It is therefore likely that the cytokine treatment induced additional changes in the tumors which contributed to their capacity to elicit the T cell response.
Nagy
N
N
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden. noemi.nagy@mtc.ki.se
Vánky
F
F
Klein
E
E
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D017951:Antigen Presentation; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007157:Immunologic Surveillance; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma