title: Restoration of the expression of transports associated with antigen processing in human malignant melanoma increases tumor-specific immunity.
abstract: The transporter associated with antigen processing (TAP) is essential for peptide delivery from the cytosol into the lumen of the endoplasmic reticulum (ER), where these peptides are loaded on HLA I molecules. Our previous study found that expressions of TAP were reduced in human malignant melanoma (MM) lesions and associated with histopathologic characteristics. In this study, we further investigate expressions of TAP and HLA class I antigen in three human MM cell lines. pEGFP-TAP1/TAP2/TAP1+TAP2 were used to restore the expressions of TAP in the antigen presentation pathway-deficient MM cell line A375. TAP1- and TAP1+TAP2-transfected A375 increased TAP1, TAP2, and HLA class I antigen expression and antigen presentation. TAP1- and TAP1+TAP2-transfected A375 exhibited a dramatic increase in Melan-A-specific cytotoxic T lymphocytes (CTLs) compared with TAP2-transfected A375 or empty vector. These CTLs were capable of killing TAP1- and TAP1+TAP2-transfected A375. TAP1+TAP2-transfected A375 generated the highest frequency of Melan-A-specific IL-12 and interferon (IFN)-gamma-producing CD8+ T cells compared with TAP1, TAP2, and empty vector. Therefore, TAP expression restores both antigen presentation and immunogenicity in A375 melanoma cells and concomitantly increases IL-12 and IFN-gamma production in tumor antigen-specific CTLs; TAP should be considered as a part of the immunotherapies for MM.
authors.affiliation: Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ye-Qiang
authors.initials: YQ
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Guan-Xin
authors.initials: GX
authors.lastname: Shen
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D018664:Interleukin-12; D007371:Interferon-gamma