Woll Petter S, Grzywacz Bartosz, Tian Xinghui, Marcus Rebecca K, Knorr David A, Verneris Michael R, Kaufman Dan S
Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Blood. 2009 Jun 11;113(24):6094-101. doi: 10.1182/blood-2008-06-165225. Epub 2009 Apr 13.
Natural killer (NK) cells serve as important effectors for antitumor immunity, and CD56+CD45+ NK cells can be routinely derived from human embryonic stem cells (hESCs). However, little is know about the ability of hESC-derived NK cells to mediate an effective in vivo antitumor response. Using bioluminescent imaging, we now demonstrate that H9 line hESC-derived NK cells mediate effective clearance of human tumor cells in vivo. In addition to increased in vitro killing of diverse tumor targets, the in vivo tumor clearance by H9 hESC-derived NK cells was more effective compared with NK cells derived from umbilical cord blood (UCB). Phenotypic analysis demonstrates the hESC-derived NK cells are uniformly CD94+CD117(low/-), an NK-cell population characterized by potent cytolytic activity and thus more competent to mediate tumor clearance. These studies demonstrate that hESCs provide an important model to study human lymphocyte development and may serve as a novel source for antitumor immunotherapy.
自然杀伤（NK）细胞是抗肿瘤免疫的重要效应细胞，并且CD56+CD45+ NK细胞通常可从人胚胎干细胞（hESC）中获得。然而，关于hESC来源的NK细胞介导有效的体内抗肿瘤反应的能力，人们了解甚少。利用生物发光成像技术，我们现在证明H9系hESC来源的NK细胞在体内可介导人肿瘤细胞的有效清除。除了增强对多种肿瘤靶标的体外杀伤作用外，与脐带血（UCB）来源的NK细胞相比，H9 hESC来源的NK细胞在体内的肿瘤清除效果更显著。表型分析表明，hESC来源的NK细胞均为CD94+CD117（低/ -），这是一种具有强大细胞溶解活性的NK细胞群体，因此更有能力介导肿瘤清除。这些研究表明，hESC为研究人类淋巴细胞发育提供了一个重要模型，并且可能成为抗肿瘤免疫治疗的新来源。
