title: Recognition and killing of cancer stem-like cell population in hepatocellular carcinoma cells by cytokine-induced killer cells via NKG2d-ligands recognition.
abstract: 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 CSCsin vitroby 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 CKAin vitroagainst 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.
authors.affiliation: Department of Oncology, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China; Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Rong
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Hong-Fen
authors.initials: HF
authors.lastname: Shen
authors.affiliation: Department of Pathology, Guilin Medical College , Guilin, China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Jia
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Rao-Ying
authors.initials: RY
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Tao-Yan
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Hao
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Yu-Shuang
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Anatomy, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering , School of Basic Medical Science, Southern Medical University , Guangzhou, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Department of Oncology, Traditional Chinese Medicine-Integrated Hospital , Southern Medical University , Guangzhou, China.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Li
authors.affiliation: Children's Hospital Boston, Harvard Medical School , Boston, MA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, Traditional Chinese Medicine-Integrated Hospital , Southern Medical University , Guangzhou, China.
authors.forename: Rong-Cheng
authors.initials: RC
authors.lastname: Luo
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
keywords: Cancer stem cells; NKG2D-ligands recognition; cytokine-induced killer cells; hepatocellular carcinoma; in vivo bioluminescence imaging; promoter-reporter gene strategy; time-lapse recording