Imaoka Yuki, Ohira Masahiro, Nakayama Toshihiro, Akabane Miho, Tajima Tetsuya, Yokota Shinichiro, Krams Sheri M, Martinez Olivia M, Esquivel Carlos O, Sasaki Kazunari, Ohdan Hideki
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Division of Abdominal Transplant, Department of Surgery, School of Medicine, Stanford University, Stanford, CA, USA.
Cell Transplant. 2024 Jan-Dec;33:9636897241283289. doi: 10.1177/09636897241283289.
This study investigated the substantial variability in the quality of liver natural killer (NK) cells from deceased donors (DDs). This study assessed liver nonparenchymal cells from 51 DDs for activation receptors and cytotoxicity against K562 (leukemia) and HepG2 (hepatoma) cell lines. The results indicated variability in TNF-related apoptosis-inducing ligand (TRAIL) and NK stimulatory receptor NK group 2 member D (NKG2D) expression in liver NK cells from DDs, which correlated with cytotoxicity against tumor cell lines. In addition, the white blood cell (WBC) count, aspartate aminotransferase (AST) level, body mass index (BMI), and platelet count were significantly associated with enhanced TRAIL and NKG2D expression. A predictive score integrating AST/platelet ratio index, BMI, and WBC count was developed to effectively identify DDs with high antitumor activity in liver NK cells. This score is expected to predict DDs with high-quality liver NK cells, which can be used for the purpose of immunotherapies.
本研究调查了已故供体(DDs)肝脏自然杀伤(NK)细胞质量的显著变异性。本研究评估了51名DDs的肝脏非实质细胞的活化受体以及对K562(白血病)和HepG2(肝癌)细胞系的细胞毒性。结果表明,DDs肝脏NK细胞中肿瘤坏死因子相关凋亡诱导配体(TRAIL)和NK刺激受体NK组2成员D(NKG2D)表达存在变异性,这与对肿瘤细胞系的细胞毒性相关。此外,白细胞(WBC)计数、天冬氨酸转氨酶(AST)水平、体重指数(BMI)和血小板计数与TRAIL和NKG2D表达增强显著相关。开发了一个综合AST/血小板比率指数、BMI和WBC计数的预测评分,以有效识别肝脏NK细胞具有高抗肿瘤活性的DDs。该评分有望预测具有高质量肝脏NK细胞的DDs,可用于免疫治疗目的。