Early hematopoietic zinc finger protein prevents tumor cell recognition by natural killer cells.
Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells.
La Rocca
Rosanna
R
Department of Experimental and Clinical Medicine G Salvatore, University of Catanzaro Magna Graecia, Catanzaro, Italy.
Fulciniti
Mariateresa
M
Lakshmikanth
Tadepally
T
Mesuraca
Maria
M
Ali
Talib Hassan
TH
Mazzei
Valerio
V
Amodio
Nicola
N
Catalano
Lucio
L
Rotoli
Bruno
B
Ouerfelli
Ouathek
O
Grieco
Michele
M
Gulletta
Elio
E
Bond
Heather M
HM
Morrone
Giovanni
G
Ferrone
Soldano
S
Carbone
Ennio
E