title: Immunoproteasome subunits LMP2 and LMP7 downregulation in primary malignant melanoma lesions: association with lack of spontaneous regression.
abstract: Recently, expression of the immunoproteasome subunits low molecular protein (LMP) 2 or LMP7 was shown to reduce the presentation of certain major histocompatibility complex (MHC) class I-restricted tumour peptide epitopes in renal cell carcinoma and melanoma cells. This may provide the tumour cells with an immune escape mechanism. To test the relevance of this hypothesis, we have taken advantage of the fact that spontaneous regression of human primary melanoma is thought to be the result of a successful peptide-specific cellular immune response in vivo. Immunohistochemical staining with anti-LMP2 and anti-LMP7 xenoantibodies showed a significantly higher expression of these immunoproteasome subunits in primary melanoma lesions exhibiting histological signs of tumour regression than in primary melanoma lesions without regression phenomena. In spontaneously regressing melanoma lesions, LMP2 and LMP7 expression was significantly associated with the presence of tumour-infiltrating lymphocytes. Our results are compatible with the possibility that the expression of the immunoproteasome subunits LMP2 and LMP7 rather than their downregulation in melanoma cells is associated with the presence of a successful anti-melanoma immune response.
authors.affiliation: Department of Dermatology, University School of Medicine, Essen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Dissemond
authors.forename: Petra
authors.initials: P
authors.lastname: Goette
authors.forename: Janet
authors.initials: J
authors.lastname: Moers
authors.forename: Anette
authors.initials: A
authors.lastname: Lindeke
authors.forename: Manfred
authors.initials: M
authors.lastname: Goos
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Stephan N
authors.initials: SN
authors.lastname: Wagner
mesh_terms: D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D008285:Major Histocompatibility Complex / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D009097:Multienzyme Complexes; D009365:Neoplasm Regression, Spontaneous / Q000276:immunology*; D009508:Nevus, Pigmented / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D009097:Multienzyme Complexes; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex