title: Cytokine-induced killer cells efficiently kill stem-like cancer cells of nasopharyngeal carcinoma via the NKG2D-ligands recognition.
abstract: Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter. Our study reported in vitro intense tumor-killing activity of CIK cells against putative CSCs of NPC, as revealed by percentage analysis of side population cells, tumorsphere formation assay and Nanog-promoter-GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time-lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs or tumorspheres were usually attacked simultaneously by many CIK cells and finally killed by CIK cells, suggesting the necessity of achieving sufficient effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D antibody significantly but partially abrogated CIK cell-mediated cytolysis against putative CSCs. More importantly, intravenous infusion of CIK cells significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable reduction in putative CSC number monitored by whole-body bioluminescence imaging. Taken together, our findings suggest that CIK cells demonstrate the intense tumor-killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands recognition. These results indicate that CIK cell-based therapeutic strategy against CSCs presents a promising and safe approach for cancer treatment.
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Rong
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Rao-Ying
authors.initials: RY
authors.lastname: Xie
authors.affiliation: Department of Pathology, Guilin Medical College, Guilin 541001, China.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Jia
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hong-Fen
authors.initials: HF
authors.lastname: Shen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Hao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Guilin Medical College, Guilin 541001, China.
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Guilin Medical College, Guilin 541001, China.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Zhou
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Tao-Yan
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Shuang
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma; D002469:Cell Separation; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020287:In Situ Nick-End Labeling; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K
keywords: cancer stem cells; cytokine-induced killer cells; nasopharyngeal carcinoma; promoter-reporter gene strategy; time-lapse imaging