Early Hematopoietic Zinc Finger (EHZF/ZNF521) prevents tumor cell recognition by Natural Killer cells. (41.43)

Abstract

Abstract EHZF/ZNF521 is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is downregulated 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 upregulation of HLA class I cell surface expression. This phenotypic change was associated with increased level of HLA class I heavy chain, in absence of detectable changes in the expression of other antigen processing machinery (APM) 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 antigen-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I antigen upregulation 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.