Expression and functional analysis of human leukocyte antigen class I antigen-processing machinery in medulloblastoma.
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.
Raffaghello
Lizzia
L
Laboratories of Oncology, G. Gaslini Institute, Genoa, Italy. lizziaraffaghello@ospedale-gaslini.ge.it
Nozza
Paolo
P
Morandi
Fabio
F
Camoriano
Marta
M
Wang
Xinhui
X
Garrè
Maria Luisa
ML
Cama
Armando
A
Basso
Giuseppe
G
Ferrone
Soldano
S
Gambini
Claudio
C
Pistoia
Vito
V
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
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I