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Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to
Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and
Function between Healthy and Cancer Patients
#MMPMID28424683
Kaur K
; Cook J
; Park SH
; Topchyan P
; Kozlowska A
; Ohanian N
; Fang C
; Nishimura I
; Jewett A
Front Immunol
2017[]; 8
(?): 297
PMID28424683
show ga
Natural killer (NK) cells are known to target cancer stem cells and
undifferentiated tumors. In this paper, we provide a novel strategy for expanding
large numbers of super-charged NK cells with significant potential to lyse and
differentiate cancer stem cells and demonstrate the differences in the dynamics
of NK cell expansion between healthy donors and cancer patients. Decline in
cytotoxicity and lower interferon (IFN)-? secretion by osteoclast (OC)-expanded
NK cells from cancer patients correlates with faster expansion of residual
contaminating T cells within purified NK cells, whereas healthy donors' OCs
continue expanding super-charged NK cells while limiting T cell expansion for up
to 60?days. Similar to patient NK cells, NK cells from tumor-bearing
BLT-humanized mice promote faster expansion of residual T cells resulting in
decreased numbers and function of NK cells, whereas NK cells from mice with no
tumor continue expanding NK cells and retain their cytotoxicity. In addition,
dendritic cells (DCs) in contrast to OCs are found to promote faster expansion of
residual T cells within purified NK cells resulting in the decline in NK cell
numbers from healthy individuals. Addition of anti-CD3 mAb inhibits T cell
proliferation while enhancing NK cell expansion; however, expanding NK cells have
lower cytotoxicity but higher secretion of IFN-?. Expansion and functional
activation of super-charged NK cells by OCs is dependent on interleukin (IL)-12
and IL-15. Thus, in this report, we not only provide a novel strategy to expand
super-charged NK cells, but also demonstrate that rapid and sustained expansion
of residual T cells within the purified NK cells during expansion with DCs or OCs
could be a potential mechanism by which the numbers and function of NK cells
decline in cancer patients and in BLT-humanized mice.
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