title: Neuroblastoma killing properties of Vδ2 and Vδ2-negative γδT cells following expansion by artificial antigen-presenting cells.
abstract: OBJECTIVE
  The majority of circulating human γδT lymphocytes are of the Vγ9Vδ2 lineage, and have T-cell receptor (TCR) specificity for nonpeptide phosphoantigens. Previous attempts to stimulate and expand these cells have therefore focused on stimulation using ligands of the Vγ9Vδ2 receptor, whereas relatively little is known about variant blood γδT subsets and their potential role in cancer immunotherapy.
  
  
  METHODS
  To expand the full repertoire of γδT without bias toward specific TCRs, we made use of artificial antigen-presenting cells loaded with an anti γδTCR antibody that promoted unbiased expansion of the γδT repertoire. Expanded cells from adult blood donors were sorted into 3 populations expressing respectively Vδ2 TCR chains (Vδ2(+)), Vδ1 chains (Vδ1(+)), and TCR of other δ chain subtypes (Vδ1(neg)Vδ2(neg)).
  
  
  RESULTS
  Both freshly isolated and expanded cells showed heterogeneity of differentiation markers, with a less differentiated phenotype in the Vδ1 and Vδ1(neg)Vδ2(neg) populations. Expanded cells were largely of an effector memory phenotype, although there were higher numbers of less differentiated cells in the Vδ1(+) and Vδ1(neg)Vδ2(neg) populations. Using neuroblastoma tumor cells and the anti-GD2 therapeutic mAb ch14.18 as a model system, all three populations showed clinically relevant cytotoxicity. Although killing by expanded Vδ2 cells was predominantly antibody dependent and proportionate to upregulated CD16, Vδ1 cells killed by antibody-independent mechanisms.
  
  
  CONCLUSIONS
  In conclusion, we have demonstrated that polyclonal-expanded populations of γδT cells are capable of both antibody-dependent and -independent effector functions in neuroblastoma.
authors.affiliation: Units of Cancer Section.
authors.forename: Jonathan P H
authors.initials: JP
authors.lastname: Fisher
authors.affiliation: Units of Cancer Section.
authors.forename: Mengyong
authors.initials: M
authors.lastname: Yan
authors.affiliation: Units of Cancer Section.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heuijerjans
authors.affiliation: Immunobiology, University College London Institute of Child Health, London, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Carter
authors.affiliation: Units of Cancer Section.
authors.forename: Ayda
authors.initials: A
authors.lastname: Abolhassani
authors.affiliation: Units of Cancer Section.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Frosch
authors.affiliation: Units of Cancer Section.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wallace
authors.affiliation: Units of Cancer Section.
authors.forename: Barry
authors.initials: B
authors.lastname: Flutter
authors.affiliation: Units of Cancer Section.
authors.forename: Anna
authors.initials: A
authors.lastname: Capsomidis
authors.affiliation: Units of Cancer Section.
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.affiliation: Units of Cancer Section, Molecular Immunology, and Immunobiology, University College London Institute of Child Health, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.affiliation: Units of Cancer Section, Molecular Immunology, and Immunobiology, University College London Institute of Child Health, London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Callard
authors.affiliation: Molecular Immunology, and.
authors.forename: Kenth
authors.initials: K
authors.lastname: Gustafsson
authors.affiliation: Units of Cancer Section, j.anderson@ucl.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Anderson
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D014644:Genetic Variation; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007133:Immunoglobulin Joining Region; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG