PMID- 16322289
OWN - NLM
STAT- MEDLINE
DCOM- 20060124
LR  - 20210103
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 23
DP  - 2005 Dec 1
TI  - Human leukocyte antigen and antigen processing machinery component defects in 
      astrocytic tumors.
PG  - 8304-11
AB  - PURPOSE: To determine the frequency of abnormalities in human leukocyte antigen 
      (HLA) and antigen processing machinery (APM) component expression in malignant 
      brain tumors. This information may contribute to our understanding of the immune 
      escape mechanisms used by malignant brain tumors because HLA antigens mediate 
      interactions of tumor cells with the host's immune system. EXPERIMENTAL DESIGN: 
      Eighty-eight surgically removed malignant astrocytic tumors, classified according 
      to the WHO criteria, were stained in immunoperoxidase reactions with monoclonal 
      antibody recognizing monomorphic, locus-specific, and allospecific determinants 
      of HLA class I antigens, beta2-microglobulin, APM components (LMP2, LMP7, TAP1, 
      TAP2, calnexin, calreticulin, and tapasin), and HLA class II antigens. RESULTS: 
      HLA class I antigens were lost in approximately 50% of the 47 glioblastoma 
      multiforme (GBM) lesions and in approximately 20% of the 18 grade 2 astrocytoma 
      lesions stained. Selective HLA-A2 antigen loss was observed in approximately 80% 
      of the 24 GBM lesions and in approximately 50% of the 12 grade 2 astrocytoma 
      lesions stained. HLA class I antigen loss was significantly (P < 0.025) 
      correlated with tumor grade. Among the APM components investigated, tapasin 
      expression was down-regulated in approximately 20% of the GBM lesions analyzed; 
      it was associated, although not significantly, with HLA class I antigen 
      down-regulation and tumor grade. HLA class II antigen expression was detected in 
      approximately 30% of the 44 lesions analyzed. CONCLUSION: The presence of HLA 
      antigen defects in malignant brain tumors may provide an explanation for the 
      relatively poor clinical response rates observed in the majority of the T 
      cell-based immunotherapy clinical trials conducted to date in patients with 
      malignant brain tumors.
FAU - Facoetti, Angelica
AU  - Facoetti A
AD  - Department of Animal Biology, University of Pavia and Center of Study for 
      Histochemistry, Consiglio Nazionale delle Ricerche, Italy.
FAU - Nano, Rosanna
AU  - Nano R
FAU - Zelini, Paola
AU  - Zelini P
FAU - Morbini, Patrizia
AU  - Morbini P
FAU - Benericetti, Eugenio
AU  - Benericetti E
FAU - Ceroni, Mauro
AU  - Ceroni M
FAU - Campoli, Michael
AU  - Campoli M
FAU - Ferrone, Soldano
AU  - Ferrone S
LA  - eng
GR  - P30 CA16056/CA/NCI NIH HHS/United States
GR  - R01 CA67108/CA/NCI NIH HHS/United States
GR  - T32 CA85183/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-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 (Antibodies, Monoclonal)
RN  - 0 (Antiporters)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Calreticulin)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (TAP1 protein, human)
RN  - 0 (beta 2-Microglobulin)
RN  - 0 (tapasin)
RN  - 139873-08-8 (Calnexin)
RN  - 144416-78-4 (LMP-2 protein)
RN  - 145892-13-3 (TAP2 protein, human)
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/metabolism
MH  - Antibodies, Monoclonal
MH  - Antigen Presentation
MH  - Antiporters/*metabolism
MH  - Astrocytoma/*metabolism/pathology
MH  - Biomarkers, Tumor/metabolism
MH  - Brain Neoplasms/*metabolism/pathology
MH  - Calnexin/metabolism
MH  - Calreticulin/metabolism
MH  - Cysteine Endopeptidases/metabolism
MH  - Down-Regulation
MH  - HLA-A2 Antigen/*metabolism
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Immunoglobulins/*metabolism
MH  - Membrane Transport Proteins
MH  - Multienzyme Complexes/metabolism
MH  - Proteasome Endopeptidase Complex
MH  - beta 2-Microglobulin/metabolism
EDAT- 2005/12/03 09:00
MHDA- 2006/01/25 09:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2006/01/25 09:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
AID - 11/23/8304 [pii]
AID - 10.1158/1078-0432.CCR-04-2588 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Dec 1;11(23):8304-11. doi: 10.1158/1078-0432.CCR-04-2588.