Novel immunotherapy using liver-derived natural killer cells for preventing hepatocellular carcinoma recurrence in liver transplantation

Abstract

Tumor recurrence is the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants. However, no prevention or treatment exists for HCC recurrence after liver transplantation. Here, we describe an adoptive immunotherapy approach that uses natural killer (NK) cells derived from both living and deceased donor liver graft perfusates. Liver NK cells exhibited the vigorous cytotoxicity against hepatoma cell line after IL-2 stimulation through the tumor necrosis factor (TNF)-related apoptosis- inducing ligand (TRAIL)-TRAIL receptor pathway. In an in vivo mouse model, adoptive transfer of TRAIL-expressing liver NK cells inhibited the growth of liver tumors. Taken together, these fi ndings suggest that we have established a method of retrieving NK cells from donor liver graft perfusate under current good manufacturing practice conditions for the treatment of liver transplant recipients with HCC. Clinical trials of adoptive immunotherapy with liver NK cells have been conducted in both living and deceased donor liver transplantations.