title: Differential expression of melanoma-associated antigens and molecules involved in antigen processing and presentation in three cell lines established from a single patient.
abstract: Tumour cells are able to evade the immune system by using several 'escape mechanisms'. Downregulation of molecules involved in the processing and presentation of self-antigens has been reported. However, these adaptations have not been compared in metastases in different anatomical locations but derived from a single patient. We investigated three melanoma cell lines--MJT1 from the parietal lobe of the brain, MJT3 from the cerebellum and MJT5 from the left side of the neck--established from biopsies excised from a 45 year old female patient. Although human leukocyte antigen (HLA) class I was detected in all three cell lines by flow cytometry using an anti-HLA monomorphic antibody, further serological analysis demonstrated HLA B38 loss in all three cell lines, HLA B7 downregulation in MJT5 (skin metastases) and B7 loss in MJT3 and MJT1 (brain metastases) compared with the HLA type of the patient's normal autologous lymphocytes. Interferon-gamma (IFNgamma) treatment increased the expression of HLA class I and transporters associated with antigen processing 1 (TAP1) in all three cell lines. De novo HLA class II molecule expression was observed after IFNgamma treatment in MJT3 and MJT5. Western blot and reverse transcription-polymerase chain reaction results revealed heterogeneity of melanoma-associated antigen (MAA) expression in the cell lines: MJT3 cells expressed higher levels of MAAs than the other two cell lines. In conclusion, this study has demonstrated that three metastatic lesions from a single patient can have differential expression of molecules involved in antigen processing (TAP1) and presentation (HLA I and II), but that expression of these molecules is modulated by IFNgamma to a similar degree in all cell lines. In contrast, the downregulation of expression of specific MAAs between the three cell lines was unaffected by the addition of IFNgamma.
authors.affiliation: Department of Oncology, St. George's Hospital Medical School, London, UK.
authors.forename: Edit
authors.initials: E
authors.lastname: Kovalcsik
authors.forename: Justin
authors.initials: J
authors.lastname: John
authors.forename: Matthew
authors.initials: M
authors.lastname: Turner
authors.forename: Lindsay
authors.initials: L
authors.lastname: Birchall
authors.forename: Deborah
authors.initials: D
authors.lastname: Sage
authors.forename: Robert
authors.initials: R
authors.lastname: Whittle
authors.forename: Angus
authors.initials: A
authors.lastname: Dalgleish
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism; D059945:HLA-B38 Antigen; D015793:HLA-B7 Antigen / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D014407:Tumor Cells, Cultured
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015235:HLA-B Antigens; D059945:HLA-B38 Antigen; D015793:HLA-B7 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; D007371:Interferon-gamma