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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2554-2561
IMMUNOBIOLOGY
Dendritic cells for NK/LAK activation: rationale for
multicellular immunotherapy in neuroblastoma patients
Dominique Valteau-Couanet,
Christophe Leboulaire,
Kim Maincent,
Muriel Tournier,
Olivier Hartmann,
Jean Bénard,
Françoise Beaujean,
Catherine Boccaccio,
Laurence Zitvogel, and
Eric Angevin
From the 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; and
the Etablissement Français du sang, Créteil, France.
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.
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