Abstract:
:Tumor recurrence is the main limitation of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants. However, there is no prevention or treatment for HCC recurrence after LT. Here we describe a clinical-scale method for an adoptive immunotherapy approach that uses natural killer (NK) cells derived from deceased donor liver graft perfusate to prevent tumor recurrence after LT. Liver mononuclear cells (LMNCs) that were extracted from deceased donor liver graft perfusate contained a high percentage of NK cells (45.0 ± 4.0%) compared with peripheral blood mononuclear cells (PBMCs) (21.8 ± 5.2%) from the same donor. The CD69 activation marker and the natural cytotoxicity receptors, NKp44 and NKp46, were expressed at high levels in freshly isolated liver NK cells. Furthermore, interleukin-2 (IL-2)-stimulated NK cells showed greater upregulation of activation markers and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell-mediated antitumor cell death and increased production of interferon. Moreover, IL-2 stimulation induced LMNCs to exhibit a strong cytotoxicity against NK-susceptible K562 target cells compared with PBMCs (p < 0.01). Finally, we also showed that the final product contained a very low T-cell contamination (0.02 ± 10(6) cells/kg(-1)), which reduces the risk of graft-versus-host disease (GVHD). Collectively, our results suggest that the adoptive transfer of IL-2-stimulated NK cells from deceased donor liver graft perfusate could be a promising treatment for LT patients with HCC.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Ohira M,Nishida S,Tryphonopoulos P,Tekin A,Selvaggi G,Moon J,Levi D,Ricordi C,Ishiyama K,Tanaka Y,Ohdan H,Tzakis AGdoi
10.3727/096368911X627589subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1397-406issue
7eissn
0963-6897issn
1555-3892pii
ct0351ohirajournal_volume
21pub_type
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pub_type: 临床试验,杂志文章,随机对照试验
doi:
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