Rong, Xiao-XiangWei, FangLin, Xiao-LinQin, Yu-JuanChen, LinWang, Hui-YanShen, Hong-FenJia, Li-TingXie, Rao-YingLin, Tao-YanHao, Wei-ChaoYang, JieYang, ShengCheng, Yu-ShuangHuang, Wen-HuaLi, Ai-minSun, YanLuo, Rong-ChengXiao, Dong2016-06-142016Rong, X., F. Wei, X. Lin, Y. Qin, L. Chen, H. Wang, H. Shen, et al. 2016. “Recognition and killing of cancer stem-like cell population in hepatocellular carcinoma cells by cytokine-induced killer cells via NKG2d-ligands recognition.” Oncoimmunology 5 (3): e1086060. doi:10.1080/2162402X.2015.1086060. http://dx.doi.org/10.1080/2162402X.2015.1086060.2162-4011http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320249ABSTRACT There is an urgent need for more potent and safer approaches to eradicate cancer stem cells (CSCs) for curing cancer. In this study, we investigate cancer-killing activity (CKA) of cytokine-induced killer (CIK) cells against CSCs of hepatocellular carcinoma (HCC). To visualize CSCs in vitro by fluorescence imaging, and image and quantify CSCs in tumor xenograft-bearing mice by bioluminescence imaging, HCC cells were engineered with CSC detector vector encoding GFP and luciferase controlled by Nanog promoter. We found that CIK cells have a strong CKA in vitro against putative CSCs of HCC, as shown by tumorsphere formation and time-lapse imaging. Additionally, time-lapse recording firstly revealed that putative CSCs were attacked simultaneously by many CIK cells and finally eradicated by CIK cells, indicating the necessity of achieving sufficient effector-to-target ratios. We firstly illustrated that anti-NKG2D antibody blocking partially but significantly inhibited CKA of CIK cells against putative CSCs. More importantly, intravenous infusion of CIK cells remarkably delayed tumor growth in mice with a significant decrease in putative CSC number monitored by bioluminescence imaging. Taken together, these findings demonstrate CKA of CIK cells against putative CSCs of HCC, at least in part, by NKG2D-ligands recognition.en-USCancer stem cellscytokine-induced killer cellshepatocellular carcinomain vivo bioluminescence imagingNKG2D-ligands recognitionpromoter-reporter gene strategytime-lapse recordingRecognition and killing of cancer stem-like cell population in hepatocellular carcinoma cells by cytokine-induced killer cells via NKG2d-ligands recognitionJournal Article2016-06-1410.1080/2162402X.2015.1086060