Activation and expansion of natural killer cells from liver cancer patients
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AbstractObjective: This study aims to characterize NK cells isolated from liver cancer patients and
compare the baseline with the expanded NK populations.
Background: Therapeutic approach to enhance anti-tumor immunity has been the recent focus
for cancer treatment. We have previously demonstrated that natural killer (NK) cell number
and activity were significantly lower and negatively correlated with granulin-epithelin
precursor (GEP) expression levels in liver cancer patients [Cheung et al. Oncoimmunology
2015]. Notably, GEP modulated the NK cell cytotoxicity through controlling expression of NK
receptor ligands, including down-regulation of tumor cell surface MICA and up-regulation of
HLA-E [Cheung et al. Cancer Immunol Res 2014]. Growth factor GEP is a hepatic cancer stem
cell marker [Cheung et al. Oncotarget 2016] with functional role on growth and drug resistance
[Wong et al. Mol Cancer Ther 2014]. GEP blockage by knockdown approach or treatment with
GEP monoclonal antibody A23 sensitized liver cancer cells to NK cytotoxicity and restored
NK activity [Cheung et al. Oncoimmunology 2016].
Methods: NK cells were isolated from PBMC using immuno-magnetic beads by depletion of
CD3 cells and selection of CD56 cells. Defined media with a combination of cytokines were
used to expand and activate the NK cells. Expanded NK populations were compared with
baseline on the functional characteristics.
Results: In the pilot study, ex vivo NK cell expansion protocols using defined media induced
30 to 500 fold expansion of CD3-CD56+ NK cells after 14-21 days of culture without feeder
cells. Expanded NK cells, when compared with baseline, exhibited enhanced expression of
activating receptors NKG2D and CD69, and cytotoxic activity against liver cancer cells further
increased by 20 to 80 fold.
Conclusion: In summary, ex vivo expansion and activation of peripheral NK cells isolated from
liver cancer patients were demonstrated. Further investigation include target to effector cell
interactions, functional efficacy and tumor homing efficiency of the expanded NK populations
against tumor bulk and cancer stem cell populations. The present study demonstrated the
feasibility on autologous / allogeneic NK infusion to boost immunity for liver cancer treatment.
All Author(s) ListSiu Tim Cheung, Phyllis F.Y. Cheung Charing C.N. Chong, Stephen L. Chan, Anthony W.H. Chan
Name of ConferenceAsia-Pacific Blood and Marrow Transplantation Group
Start Date of Conference28/06/2017
End Date of Conference30/06/2017
Place of ConferenceSingapre General Hospital Campus
Country/Region of ConferenceSingapore
Year2016
LanguagesEnglish-United States

Last updated on 2018-18-01 at 03:07