title: Human glioblastoma stem-like cells are more sensitive to allogeneic NK and T cell-mediated killing compared with serum-cultured glioblastoma cells.
abstract: Glioblastoma multiforme (GBM) is the most dramatic primary brain cancer with a very poor prognosis because of inevitable disease recurrence. The median overall survival is less than 1 year after diagnosis. Cancer stem cells have recently been disclosed in GBM. GBM stem-like cells (GSCs) exhibit resistance to radio/chemotherapeutic treatments and are therefore considered to play an important role in disease recurrence. GSCs are thus appealing targets for new treatments for GBM patients. In this study, we show that GBM cells with stem cell characteristics are resistant to lysis mediated by resting natural killer (NK) cells because of the expression of MHC class I molecules. However, GSCs are killed by lectin-activated NK cells. Furthermore, in experiments using the therapeutic antibody CetuximAb, we show that GSCs are sensitive to antibody-mediated cytotoxicity. We confirm the sensitivity of GSC to cytotoxicity carried out by IL2-activated NK cells and tumor-specific T cells. More importantly, we show that GSCs are more sensitive to NK and T cell-mediated lysis relatively to their corresponding serum-cultured GBM cells obtained from the same initial tumor specimen. Altogether, these results demonstrate the sensitivity of GSC to immune cell cytotoxicity and, therefore, strongly suggest that GSCs are suitable target cells for immunotherapy of GBM patients.
authors.affiliation: Département de Biologie, Centre Eugène Marquis, Rennes, France. t.avril@rennes.unicancer.fr
authors.forename: Tony
authors.initials: T
authors.lastname: Avril
authors.forename: Elodie
authors.initials: E
authors.lastname: Vauleon
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Hamlat
authors.forename: Stéphan
authors.initials: S
authors.lastname: Saikali
authors.forename: Amandine
authors.initials: A
authors.lastname: Etcheverry
authors.forename: Caroline
authors.initials: C
authors.lastname: Delmas
authors.forename: Sylma
authors.initials: S
authors.lastname: Diabira
authors.forename: Jean
authors.initials: J
authors.lastname: Mosser
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D018874:Spheroids, Cellular; D016176:T-Lymphocyte Subsets / Q000473:pathology*
chemical_list: D016895:Culture Media, Serum-Free