title: The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture.
abstract: BACKGROUND
  Chemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma (HB) and paediatric hepatocellular carcinoma (HCC). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies.
  
  
  OBJECTIVE
  Cytotoxic-immune-cells-like natural killer (NK) and T cells are major player in the defence against developing tumours. This study aimed to specifically analyse the ability of ex-vivo expanded γδ T cells to recognise and lyse HB and HCC cell lines in coculture assays.
  
  
  METHODS
  Cell viability after treatment with γδ T cells was evaluated with two HB (HUH6 and HepT1) and one HCC cell line (HC-AFW1) using a MTT-based cytotoxicity assay. The binding of T cells to target cells was monitored using immunofluorescence microscopy.
  
  
  RESULTS
  Incubation of hepatic tumour cell lines with γδ T cells led to a significant decrease in tumour cell viability. This was enhanced by zoledronic acid and histone deacetylase inhibitors. MT110, an EpCAM/CD3-bispecific BiTE antibody could bluntly enhance tumour cell lysis close to completion. γδ T cells efficiently interacted with HB and HCC cells in a spheroid culture model.
  
  
  CONCLUSIONS
  Bispecific antibodies such as MT110 might be used to intensify the antitumoural effect of γδ T cells in context of adoptive immune cell transfer. Optimised immunotherapeutic strategies might therefore improve the outcome of high risk hepatoblastoma and hepatocellular carcinoma.
authors.affiliation: Department of Paediatric Surgery and Urology, University Childreǹs Hospital, Tuebingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoh
authors.forename: Alexander
authors.initials: A
authors.lastname: Dewerth
authors.forename: Fabian
authors.initials: F
authors.lastname: Vogt
authors.forename: Julia
authors.initials: J
authors.lastname: Wenz
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Baeuerle
authors.forename: Steven W
authors.initials: SW
authors.lastname: Warmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Fuchs
authors.forename: Sorin
authors.initials: S
authors.lastname: Armeanu-Ebinger
mesh_terms: D018033:Antibodies, Bispecific / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology; D000071858:Epithelial Cell Adhesion Molecule; D018197:Hepatoblastoma / Q000276:immunology / Q000473:pathology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000494:pharmacology; D018874:Spheroids, Cellular; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000077211:Zoledronic Acid
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D004164:Diphosphonates; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D056572:Histone Deacetylase Inhibitors; D007093:Imidazoles; C509173:MT110 monoclonal antibody; D016692:Receptors, Antigen, T-Cell, gamma-delta; D057127:Single-Chain Antibodies; D000077211:Zoledronic Acid