PMID- 15814633
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20201226
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 7
DP  - 2005 Apr 1
TI  - Defects in the human leukocyte antigen class I antigen processing machinery in 
      head and neck squamous cell carcinoma: association with clinical outcome.
PG  - 2552-60
AB  - PURPOSE: Human leukocyte antigen (HLA) class I antigen defects, which are 
      frequently present in head and neck squamous cell carcinoma (HNSCC) cells may 
      provide the tumor with an escape mechanism from immune surveillance. Scanty 
      information is available about mechanisms underlying HLA class I antigen defects 
      in both lesions and cell lines from HNSCC. In this study, we investigate the role 
      of antigen processing machinery (APM) component abnormalities in the generation 
      of deficient HLA class I surface expression of HNSCC cells. EXPERIMENTAL DESIGN: 
      Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the 
      expression of the IFN-gamma inducible proteasome subunits and of the peptide 
      transporter TAP with that of HLA class I antigens in biopsies and cell lines from 
      primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA 
      class I antigen expression in surgically removed lesions were correlated with the 
      course of the disease in order to assess the clinical significance of deficient 
      expression of these molecules. RESULTS: A high frequency of LMP2, LMP7, and TAP1 
      down-regulation or loss was found in tumor lesions and cell lines obtained from 
      HNSCC cancer patients. These defects could be corrected by incubating cells with 
      IFN-gamma. Furthermore, LMP2, LMP7, TAP1, TAP2, and HLA class I antigen 
      expression rates in primary HNSCC lesions were found to predict overall survival. 
      Lastly, the level of LMP7 expression was significantly associated with disease 
      recurrence at 2 years. CONCLUSIONS: Our results suggest that the analysis of APM 
      component expression in HNSCC lesions can provide useful prognostic information 
      in patients with HNSCC.
FAU - Meissner, Markus
AU  - Meissner M
AD  - Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany.
FAU - Reichert, Torsten E
AU  - Reichert TE
FAU - Kunkel, Martin
AU  - Kunkel M
FAU - Gooding, William
AU  - Gooding W
FAU - Whiteside, Theresa L
AU  - Whiteside TL
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Seliger, Barbara
AU  - Seliger B
LA  - eng
GR  - P0-1DE 12321/DE/NIDCR NIH HHS/United States
GR  - R01CA67108/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  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (TAP1 protein, human)
RN  - 144416-78-4 (LMP-2 protein)
RN  - 145892-13-3 (TAP2 protein, human)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (LMP7 protein)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/analysis/genetics
MH  - Adult
MH  - Aged
MH  - Blotting, Western
MH  - Carcinoma, Squamous Cell/genetics/metabolism/*pathology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cysteine Endopeptidases/analysis/genetics
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - HLA Antigens/*analysis/genetics
MH  - Head and Neck Neoplasms/genetics/metabolism/*pathology
MH  - Histocompatibility Antigens Class I/analysis/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Interferon-gamma/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Multienzyme Complexes/analysis/genetics
MH  - Proteasome Endopeptidase Complex
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Tumor Cells, Cultured
EDAT- 2005/04/09 09:00
MHDA- 2005/08/09 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
AID - 11/7/2552 [pii]
AID - 10.1158/1078-0432.CCR-04-2146 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Apr 1;11(7):2552-60. doi: 10.1158/1078-0432.CCR-04-2146.