title: Expression and functional analysis of human leukocyte antigen class I antigen-processing machinery in medulloblastoma.
abstract: Defects in the expression and/or function of the human leukocyte antigen (HLA) class I antigen-processing machinery (APM) components are found in many tumor types. These abnormalities may have a negative impact on the interactions of tumor cells with host's immune system and on the outcome of T cell-based immunotherapy. To the best of our knowledge, no information is available about APM component expression and functional characteristics in human medulloblastoma cells (Mb). Therefore, in the present study, we have initially compared the expression of APM components in Mb, an embryonal pediatric brain tumor with a poor prognosis, with that in noninfiltrating astrocytic pediatric tumors, a group of differentiated brain malignancies with favorable prognosis. LMP2, LMP7, calnexin, beta2-microglobulin-free heavy chain (HC) and beta2-microglobulin were down-regulated or undetectable in Mb lesions, but not in astrocytic tumors or normal fetal cerebellum. Two Mb cell lines (DAOI and D283) displayed similar but not superimposable defects in APM component expression as compared with primary tumors. To assess the functional implications of HLA class I APM component down-regulation in Mb cell lines, we tested their recognition by HLA class I antigen-restricted, tumor antigen (TA)-specific CTL, generated by stimulations with dendritic cells that had been transfected with Mb mRNA. The Mb cell lines were lysed by TA-specific CTL in a HLA-restricted manner. Thus, defective expression of HLA class I-related APM components in Mb cells does not impair their ability to present TA to TA-specific CTL. In conclusion, these results can contribute to optimize T cell-based immunotherapeutic strategies for Mb treatment.
authors.affiliation: Laboratories of Oncology, G. Gaslini Institute, Genoa, Italy. lizziaraffaghello@ospedale-gaslini.ge.it
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.forename: Marta
authors.initials: M
authors.lastname: Camoriano
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Garrè
authors.forename: Armando
authors.initials: A
authors.lastname: Cama
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D017951:Antigen Presentation; D001932:Brain Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000276:immunology; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000276:immunology; D015236:HLA-C Antigens / Q000096:biosynthesis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I