*Purpose: Abdominal aorta calcification (AAC) is associated with an increased relative risk of coronary events, cerebrovascular events, cardiovascular events, and cardiovascular death. We report that both recipient and donor AAC are independent unfavorable prognostic factors in liver transplantation (hepatectomy). Furthermore, AAC has had a strong relationship with poor overall survival and recurrence-free survival after hepatectomy for hepatocellular carcinoma in our department. However, there has been no study on the relationship between AAC and anti-tumor immune cells in the liver. The aim of this study was to clarify the effect of atherosclerosis on intrahepatic immunity, especially on anti-tumor effects in a mouse model. We focused on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activity of liver-resident natural killer (lr-NK) cells.

*Methods: (1) The lr-NK cell activity was evaluated using flow cytometry and a cytotoxicity test and compared between two models: a mouse model of atherosclerosis (ApoE KO mice) and a wild-type mouse model (C57BL/6J) of no atherosclerosis (B6 mice).(2) The lr-NK cell activity after 30% partial hepatectomy (PH) in both models was evaluated using flow cytometry.(3) Liver metastatic growth was evaluated in both models after 2×10⁶ Hepa1-6 cells were injected in the spleens of both strains of mice that underwent 30% PH.

*Results: (1) The proportion of NK cells in the liver decreased in the atherosclerosis model. The TRAIL expression of lr-NK cells was 66.8 ± 6.1% in B6 mice and 42.6 ± 12.7% in ApoE KO mice, as determined using flow cytometry (p<0.01). The cytotoxicity of lr-NK cells against Hepa1-6 cells also significantly decreased in ApoE KO mice compared with B6 mice.(2) The TRAIL expression of lr-NK cells after PH was 42.7 ± 15.2% in B6 mice and 7.0 ± 5.9% in ApoE KO mice, as determined using flow cytometry (p<0.01).(3) Many metastatic lesions were detected in the livers of ApoE KO mice, while no metastatic lesions were detected in those of B6 mice.

*Conclusions: We have demonstrated in a mouse model that calcification of the aorta decreases NK cell activity in the liver. Combined with our findings that AAC in liver transplant donors is associated with activation of lr-NK cells (unpublished data), these data suggest that AAC reduces intrahepatic antitumor activity after liver transplantation.

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