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2017 ; 8
(34
): 57024-57038
Nephropedia Template TP
gab.com Text
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English Wikipedia
Programmed differentiated natural killer cells kill leukemia cells by engaging
SLAM family receptors
#MMPMID28915651
Wu Y
; Li Y
; Fu B
; Jin L
; Zheng X
; Zhang A
; Sun R
; Tian Z
; Wei H
Oncotarget
2017[Aug]; 8
(34
): 57024-57038
PMID28915651
show ga
Natural killer (NK) cells are important innate immune cells that can directly
kill transformed or virus-infected cells. The adoptive transfer of NK cells has
been used to treat hematological malignancies; however, the limited sources and
quantities of NK cells have restricted their clinical application. Here, we
acquired sufficient quantities of functional NK cells from CD34(+) cells treated
with a cytokine cocktail. Microarray analysis of the cultured cells revealed a
two-stage pattern of programmed differentiation during NK cell development.
Different transcription factors were enriched during these two stages, suggesting
that preparation of progenitors committed to the NK cell lineage occurs in
program 1, while NK cell transformation and maturation occur in program 2.
Cultured NK cells highly expressed signaling lymphocytic activation molecule
(SLAM) family receptors (SFRs), while leukemia cells expressed SFR ligands. The
engagement of these SFRs strengthened the cytotoxicity of NK cells toward
leukemia cells. These results demonstrate a simple method of obtaining sufficient
NK cells for clinical application, and have categorized NK cell differentiation
according to commitment and transformation programs. Moreover, the binding
between SFRs on NK cells and their ligands on leukemia cells suggests a new basis
for NK cell therapy for treatment of leukemia.