Biology Reference
In-Depth Information
relapse was 9% at 10 years post-HSCT compared with 42% in patients who
did not reactivate CMV, and CMV reactivation was not detrimental to over-
all survival. It is also possible that the lower risk of relapse reported in UCB
transplantation
[137]
is associated with CMV reactivation. CMV infection
may induce expression of a ligand that activates CD8
+
T cells and/or NK
cells. Alternatively, the virus may act as an oncolytic virus by infecting
leukemic blasts and eliminating them. In recipients of UCB HSCT, CMV
reactivation has been shown to induce a more rapid reconstitution of fully
functional, educated NK cells with increased survival capacity and the abil-
ity to respond rapidly with cytokines
[42]
. In the absence of CMV reactiva-
tion, NK cells remain immature and recovery of full effector functions takes
at least 1 year. As we continue to understand the NK cell response to human
CMV, carefully monitored CMV reactivation may actually be beneficial.
Concluding remarks
Ever since their initial identification by their ability to spontaneously reject
BM allografts and lyse cells with low MHC class I expression without prior
sensitization, NK cells have been considered important effector cells in
eliminating aberrant cells. In the clinical setting, NK cells, both in the con-
text of HSCT and adoptively transferred, have been shown to have immense
therapeutic properties, including enhancing engraftment, decreasing both
rejection and GVHD, and eliminating leukemic cells. The use of animal
models and
in vitro
assays to demonstrate NK cell effectiveness at eliminat-
ing cancer cells have been invaluable. Further characterization and identi-
fication of NK cell receptors and their ligands on tumor cells will enable a
clearer understanding of how NK cells recognize tumors and how this can
be exploited in the clinical setting. As not all tumors respond to NK cells
in the same manner, certain NK cell therapies may be more applicable to
certain cancers. Furthermore, combinations of different therapies may be
essential to enhance the efficacy of NK cell immunotherapy
in vivo.
Despite
their discovery over 40 years ago, new and exciting areas of NK cell biology
are continually emerging. The effective use of NK cells to treat cancer will
only increase as we further our understanding of how NK cells gain func-
tion, how the multitude of receptors expressed by NK cells control function,
and how we can exploit this to eliminate tumors.
350
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