title: Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients.
abstract: Natural killer (NK)/lymphokine-activated killer (LAK) cell-based immunotherapy could be beneficial against major histocompatibility complex class I-negative tumor residual disease such as neuroblastoma (NB), provided that interleukin 2 (IL-2) or surrogate nontoxic NK cell stimulatory factors could sustain NK cell activation and survival in vivo. Here we show that human monocyte-derived dendritic cells (MD-DCs) promote potent NK/LAK effector functions and long-term survival, circumventing the need for IL-2. This study demonstrates (1) the feasibility of differentiating granulocyte colony-stimulating factor-mobilized hematopoietic peripheral blood stem cells (PBSCs) into high numbers of functional MD-DCs and NK/LAK cells in a series of 12 children with stage 4 neuroblastoma (NB); (2) potent DC-mediated NK cell activation in autologous settings; (3) the reciprocal capacity of NK/LAK cells to turn immature DCs into maturing cells electively capable of triggering NK cell functions; and (4) the unique capacity of maturing DCs to sustain NK cell survival, superior to that achieved in IL-2. These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell-based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation.
authors.affiliation: Département de Pédiatrie, the Unité d'Immunologie, the Unité de Thérapie Cellulaire, and the Service de Génétique, Département de Biologie Clinique, Institut Gustave Roussy, Villejuif, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboulaire
authors.forename: Kim
authors.initials: K
authors.lastname: Maincent
authors.forename: Muriel
authors.initials: M
authors.lastname: Tournier
authors.forename: Olivier
authors.initials: O
authors.lastname: Hartmann
authors.forename: Jean
authors.initials: J
authors.lastname: Bénard
authors.forename: Françoise
authors.initials: F
authors.lastname: Beaujean
authors.forename: Catherine
authors.initials: C
authors.lastname: Boccaccio
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
mesh_terms: D002470:Cell Survival / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*