title: Human U87 glioblastoma cells with stemness features display enhanced sensitivity to natural killer cell cytotoxicity through altered expression of NKG2D ligand.
abstract: BACKGROUND
  Glioblastoma (GBM) is one of the most lethal tumors with a poor prognosis. Its inevitable recurrence is frequently explained by the presence of cancer stem cells. We aimed to show that human GBM cells with stemness features are more sensitive to natural killer (NK) cells than GBM cells without stemness characteristics.
  
  
  METHODS
  Natural killer cell cytotoxicity was measured using flow cytometry in neurosphere-forming U87 GBM cells cultured with neurobasal media (NBE condition) and compared with that in serum-cultured U87 GBM cells (serum condition). Cytotoxicity was examined after addition of blocking NKG2D monoclonal antibodies. The expression profile of NK ligands of NK cells were investigated by reverse transcription polymerase chain reaction and western blot analysis in the U87 GBM cells in both conditions.
  
  
  RESULTS
  NBE U87 cells showed higher cytotoxicity to NK cells than serum U87 cells did (55 vs 35% at an effector to target cell ratio of 5:1). The increased cytotoxicity was diminished in NBE U87 cells by a larger gap than in serum U87 cells by adding NKG2D blocking antibodies. Of the NKG2D ligands, the expression of ULBP1 and ULBP3 was relatively increased in NBE U87 cells compared to serum U87 cells.
  
  
  CONCLUSIONS
  U87 GBM cells with stemness features demonstrate increased cytotoxicity to NK cells in association with altered NKG2D ligand expression of NK cell activating receptor. Applying immune modulation to GBM treatment may be a promising adjuvant therapy in patients with intractable GBM.
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Jung-In
authors.initials: JI
authors.lastname: Yang
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Ok
authors.initials: O
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Ahn
authors.affiliation: Department of Obstetrics and Gynecology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Woo Dae
authors.initials: WD
authors.lastname: Kang
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Kyung-Sub
authors.initials: KS
authors.lastname: Moon
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Jeollanam-do South Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Duck
authors.initials: D
authors.lastname: Cho
keywords: Cancer stem cells; Glioblastoma; Immunotherapy; Natural killer cell; U87