Liver natural killer cell inoculum for liver transplantation with hepatocellular carcinoma.
OBJECTIVE
Natural killer (NK) cells are innate immune lymphocytes. NK cells contribute to host antimicrobial and antitumor immunity. Liver transplantation in patients with hepatocellular carcinoma (HCC) has increased recently. The possibility of NK cell immunotherapy for liver cancer has been studied.


RESULTS
Adoptive transfer of interleukin-2 (IL-2)-stimulated NK cells extracted from donor liver perfusate could increase an antitumor response without causing toxicity against 1-haplotype identical recipient intact tissues in patients with live donor liver transplant. Donor liver NK cells showed the most vigorous cytotoxicity against an HCC after in-vitro IL-2 stimulation, compared with donor and recipient peripheral blood NK cells and recipient liver NK cells. IL-2 stimulation led to an increased expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on liver NK cells. T-cell contamination and risk of graft-versus-host disease can be minimized with a T-cell depleting agent such as anti-CD3 antibody.


CONCLUSIONS
Allogeneic NK cells might have an advantage for adoptive immunotherapy. Liver NK cells from a deceased donor liver can be used safely as adoptive immunotherapy under current good manufacturing practice conditions for the treatment of liver transplantation with HCC. IL-2-stimulated liver NK cells have strong cytotoxicity, express TRAIL and secret interferon-γ.
aDepartment of Surgery, Miami Transplant Institute, University of Miami, Miami, Florida, bTransplant center, Carolina Healthcare system, Charlotte, North Carolina cTransplant center, Cleveland Clinic Florida, Weston, Florida, USA.
Seigo
S
Nishida
David M
DM
Levi
Andreas G
AG
Tzakis
D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000601:surgery / Q000628:therapy*; D016031:Liver Transplantation
D007376:Interleukin-2