Impact of interferons on the expression of melanoma-associated antigens in melanoma short-term cell cultures.
Some immunotherapeutic approaches based on melanoma-associated antigens rely on in vitro cultivation of melanoma cells. A beneficial effect of interferons has been shown in melanoma. This study aimed to determine whether stimulation of patient-derived melanoma short-term cell cultures using interferon-alpha and -gamma changes the expression pattern of melanoma-associated antigens. Lymph node, skin and brain metastases were cultivated for up to 3 weeks and treated with interferon-alpha, interferon-gamma or mock stimulation. Expression of the melanoma-associated antigens MAGE-3, MelanA/MART-1 and tyrosinase was determined by flow cytometry and compared with the expression pattern of HLA class I molecules. We found consistently enhanced expression of HLA class I molecules, whereas the melanoma-associated antigens showed mixed responses, with moderate induction, suppression or no visible effect. The reaction to interferon stimulation was similar for all the antigens examined within a single melanoma cell culture. In contrast to the HLA class I molecules, which showed induced expression with interferon, the melanoma-associated antigens showed a varied response to interferon stimulation. Differential reaction to interferon stimulation is of importance to immunotherapeutic modalities and might influence progression of the disease. We therefore suggest that evaluation of variation in melanoma-associated antigen expression in the clinical setting may help to identify patients who would profit from adjuvant interferon therapy.
Hofbauer
G F
GF
Department of Dermatology, University Hospital, Gloriastrasse 31, CH-8091 Zurich, Switzerland.
Geertsen
R
R
Laine
E
E
Burg
G
G
Dummer
R
R
D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens / Q000096:biosynthesis*; D000951:Antigens, Neoplasm; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology*; D008207:Lymphatic Metastasis; D058965:MART-1 Antigen; D008545:Melanoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D058951:gp100 Melanoma Antigen
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D016898:Interferon-alpha; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; C489519:Mageb3 protein, mouse; D008562:Membrane Glycoproteins; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma; D007372:Interferons; D014442:Monophenol Monooxygenase