The existing methods to avert or address the return of hepatocellular carcinoma (HCC) after liver transplantation (LT) have not proven effective. Post-LT immunosuppressive protocols tend to conserve elements of innate immunity over those of adaptive immunity. Enhancing Natural Killer (NK) cells, crucial to innate immunity, is a promising approach to combat HCC after LT. It is proposed that administering NK cells residing in the liver, obtained from the liver donor's perfusate, might have a therapeutic effect against cancer while preserving the healthy tissues of the recipient.
In an investigation involving 99 individuals who met Japan criteria preoperatively, the subset whose post-surgical pathology exceeded the Milan criteria (42 patients) experienced significantly lower recurrence-free survival rates compared to those who met the criteria (57 patients) (p=0.022). Within the group not adhering to the Milan criteria, the 17 patients treated with NK cell therapy exhibited notable improvements in recurrence-free survival. Following the NK cell infusion, an increase in both the cytotoxic capability of NK cells and the proportion of TRAIL+ NK cells in the patient's bloodstream was significant (p<0.05). The donor-derived NK cells remained detectable in the recipients' circulation for up to a month post-infusion, as determined by chimerism analysis. This procedure was also applied to recipients of deceased donor liver transplants (DDLT) in collaboration with the University of Miami starting in 2009. The phase I trial included 17 participants, with a mean follow-up duration of 96 months, and no related adverse events were reported. Patients receiving higher doses of NK cells demonstrated a significantly enhanced survival rate in comparison to those receiving lower doses (p = 0.0064). Of the DDLT cohort for HCC, 9 out of 17 patients who were within Milan criteria based on preoperative imaging found to exceed these criteria upon postoperative assessment. However, none have shown recurrence of HCC thus far.
In conclusion, IL-2 activated NK cells derived from both living and deceased donor liver grafts have been administered safely, signifying an encouraging new complementary immune therapy post-LT for HCC patients. Multi-center phase II trials are in the preparatory stages in both Japan and the USA.