PMID- 15070694
OWN - NLM
STAT- MEDLINE
DCOM- 20040527
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 8
DP  - 2004 Apr 15
TI  - Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in 
      leukemic cells: an escape mechanism from CTL and NK attack?
PG  - 3122-30
AB  - Human leukocyte antigen (HLA) class I antigen defects may have a negative impact 
      on the growing application of T-cell-based immunotherapeutic strategies for 
      treatment of leukemia. Therefore in the present study, taking advantage of a 
      large panel of HLA class I allele-specific human monoclonal antibodies, we have 
      compared HLA class I antigen expression on leukemic cells with that on autologous 
      and allogeneic normal cells. Down-regulation of HLA-A and/or -B allospecificities 
      was present in the majority of the patients studied. However, down-regulation did 
      not affect all HLA class I alleles uniformly, but was almost exclusively 
      restricted to HLA-A allospecificities and to HLA-B allospecificities which belong 
      to the HLA-Bw6 group. The latter allospecificities, at variance from those that 
      belong to the HLA-Bw4 group, do not modulate the interactions of leukemic cells 
      with natural killer (NK) cells. Therefore, our results suggest that the selective 
      down-regulation of HLA-A and HLA-Bw6 allospecificities associated with HLA-Bw4 
      preservation provides leukemic cells with an escape mechanism not only from 
      cytotoxic T lymphocytes (CTLs), but also from NK cells. As a result T-cell-based 
      immunotherapeutic strategies for leukemia should utilize HLA-Bw4 alloantigens as 
      restricting elements since a selective HLA-Bw4 allele loss would provide leukemic 
      cells with an escape mechanism from CTLs, but would increase their susceptibility 
      to NK cell-mediated lysis.
FAU - Demanet, Christian
AU  - Demanet C
AD  - HLA Laboratory, Academic Hospital VUB, Brussels, Belgium. 
      christian.demanet@az.vub.ac.be
FAU - Mulder, Arend
AU  - Mulder A
FAU - Deneys, Veronique
AU  - Deneys V
FAU - Worsham, Maria J
AU  - Worsham MJ
FAU - Maes, Piet
AU  - Maes P
FAU - Claas, Frans H
AU  - Claas FH
FAU - Ferrone, Soldano
AU  - Ferrone S
LA  - eng
GR  - CA37959/CA/NCI NIH HHS/United States
GR  - CA67108/CA/NCI NIH HHS/United States
GR  - P30 CA16056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031204
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (HLA-Bw6 antigen)
SB  - IM
MH  - Alleles
MH  - Antibodies, Monoclonal
MH  - Antibody Specificity
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Gene Expression
MH  - HLA-A Antigens/genetics/*metabolism
MH  - HLA-B Antigens/genetics/*metabolism
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Leukemia/genetics/*immunology
MH  - Mutation
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2004/04/09 05:00
MHDA- 2004/05/28 05:00
CRDT- 2004/04/09 05:00
PHST- 2004/04/09 05:00 [pubmed]
PHST- 2004/05/28 05:00 [medline]
PHST- 2004/04/09 05:00 [entrez]
AID - S0006-4971(20)43811-X [pii]
AID - 10.1182/blood-2003-07-2500 [doi]
PST - ppublish
SO  - Blood. 2004 Apr 15;103(8):3122-30. doi: 10.1182/blood-2003-07-2500. Epub 2003 Dec 
      4.