title: A melanoma immune response signature including Human Leukocyte Antigen-E.
abstract: Paired cultures of early-passage melanoma cells and melanocytes were established from metastatic lesions and the uninvolved skin of five patients. In this stringent autologous setting, cDNA profiling was used to analyze a subset of 1477 genes selected by the Gene Ontology term 'immune response'. Human Leukocyte Antigen E (HLA-E) was ranked 19th among melanoma-overexpressed genes and was embedded in a transformation signature including its preferred peptide ligand donors HLA-A, HLA-B, HLA-C, and HLA-G. Mostly undetectable in normal skin and 39 nevi (including rare and atypical lesions), HLA-E was detected by immunohistochemistry in 17/30 (57%) and 32/48 (67%) primary and metastatic lesions, respectively. Accordingly, surface HLA-E was higher on melanoma cells than on melanocytes and protected the former (6/6 cell lines) from lysis by natural killer (NK) cells, functionally counteracting co-expressed triggering ligands. Although lacking HLA-E, melanocytes (4/4 cultures) were nevertheless (and surprisingly) fully protected from NK cell lysis.
authors.affiliation: Laboratory of Immunology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tremante
authors.forename: Agnese
authors.initials: A
authors.lastname: Ginebri
authors.forename: Elisa
authors.initials: E
authors.lastname: Lo Monaco
authors.forename: Barbara
authors.initials: B
authors.lastname: Benassi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Frascione
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.forename: Sandra
authors.initials: S
authors.lastname: Cappellacci
authors.forename: Caterina
authors.initials: C
authors.lastname: Catricalà
authors.forename: Diego
authors.initials: D
authors.lastname: Arcelli
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Natali
authors.forename: Franco
authors.initials: F
authors.lastname: Di Filippo
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Paolo
authors.initials: P
authors.lastname: Visca
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
authors.forename: Patrizio
authors.initials: P
authors.lastname: Giacomini
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: HLA-E; NK cells; cDNA arrays; melanocytes; melanoma