Clinical-Scale Isolation of Interleukin-2-Stimulated Liver Natural Killer Cells for Treatment of Liver Transplantation with Hepatocellular Carcinoma
Autor: | David Levi, Andreas G. Tzakis, Masahiro Ohira, Hideki Ohdan, Kohei Ishiyama, Gennaro Selvaggi, Seigo Nishida, Yuka Tanaka, Camillo Ricordi, Panagiotis Tryphonopoulos, Akin Tekin, Jang Moon |
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Rok vydání: | 2012 |
Předmět: |
Adult
Antigens Differentiation T-Lymphocyte Graft Rejection Male Interleukin 2 Adoptive cell transfer Carcinoma Hepatocellular Liver cytology medicine.medical_treatment Biomedical Engineering lcsh:Medicine Apoptosis Biology Liver transplantation Natural killer cell TNF-Related Apoptosis-Inducing Ligand Young Adult Interleukin 21 Antigens CD Secondary Prevention medicine Humans Lectins C-Type Aged Transplantation Lymphokine-activated killer cell Natural Cytotoxicity Triggering Receptor 2 Natural Cytotoxicity Triggering Receptor 1 Liver Neoplasms lcsh:R Cell Biology Middle Aged Tissue Donors Liver Transplantation Up-Regulation Killer Cells Natural medicine.anatomical_structure Liver Immunology Leukocytes Mononuclear Interleukin 12 Cancer research Cytokines Interleukin-2 Female Immunotherapy K562 Cells medicine.drug |
Zdroj: | Cell Transplantation, Vol 21 (2012) |
ISSN: | 1555-3892 0963-6897 |
Popis: | 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 ± 106 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. |
Databáze: | OpenAIRE |
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