PMID- 15897905
OWN - NLM
STAT- MEDLINE
DCOM- 20050802
LR  - 20210102
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 29
DP  - 2005 Jul 7
TI  - Multiple defects of the antigen-processing machinery components in human 
      neuroblastoma: immunotherapeutic implications.
PG  - 4634-44
AB  - Low expression of human leukocyte antigen (HLA) class I in human tumors may be 
      related to defects of the antigen-processing machinery (APM) components. 
      Neuroblastoma cells are virtually HLA class I negative, but (i) the underlying 
      mechanisms are unknown, and (ii) expression of the APM components has never been 
      investigated. Here we have used a panel of novel monoclonal antibodies to 
      proteasomal and immunoproteasomal components, chaperons and transporter 
      associated with antigen processing (TAP) to characterize 24 stroma-poor 
      neuroblastoma tumors and six neuroblastoma cell lines. Primary tumors showed 
      defects in the expression of zeta, tapasin, TAP1 or TAP2, HLA class I heavy chain 
      and beta2 microglobulin, LMP2 and LMP7, as compared to normal adrenal medulla. 
      Neuroblastoma cell lines displayed roughly similar patterns of APM expression in 
      comparison to primary tumors. Incubation of neuroblastoma cell lines with 
      interferon-gamma caused upregulation of HLA class I molecules and reduced lysis 
      by killer inhibitory receptor HLA ligand-matched NK cells. Defects in APM 
      components explain reduced peptide loading on HLA class I molecules, their 
      instability and failure to be expressed on the cell surface. HLA class I 
      upregulation by interferon-gamma, although enhancing neuroblastoma cell 
      recognition by cytotoxic T cells, dampens their susceptibility to NK cells.
FAU - Raffaghello, Lizzia
AU  - Raffaghello L
AD  - Laboratory of Oncology, G Gaslini Institute, Largo G Gaslini, Genova, Italy. 
      lizziaraffaghello@ospedale-gaslini.ge.it
FAU - Prigione, Ignazia
AU  - Prigione I
FAU - Bocca, Paola
AU  - Bocca P
FAU - Morandi, Fabio
AU  - Morandi F
FAU - Camoriano, Marta
AU  - Camoriano M
FAU - Gambini, Claudio
AU  - Gambini C
FAU - Wang, Xinhui
AU  - Wang X
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Pistoia, Vito
AU  - Pistoia V
LA  - eng
GR  - R01 CA 67108/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA Antigens)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Child
MH  - Child, Preschool
MH  - Down-Regulation
MH  - Female
MH  - Genes, MHC Class I
MH  - HLA Antigens/*biosynthesis
MH  - Humans
MH  - Infant
MH  - Interferon-gamma/*biosynthesis
MH  - Male
MH  - Neuroblastoma/*immunology/pathology
MH  - Stromal Cells
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2005/05/18 09:00
MHDA- 2005/08/03 09:00
CRDT- 2005/05/18 09:00
PHST- 2005/05/18 09:00 [pubmed]
PHST- 2005/08/03 09:00 [medline]
PHST- 2005/05/18 09:00 [entrez]
AID - 1208594 [pii]
AID - 10.1038/sj.onc.1208594 [doi]
PST - ppublish
SO  - Oncogene. 2005 Jul 7;24(29):4634-44. doi: 10.1038/sj.onc.1208594.