Dendritic cells for NK/LAK activation:: rationale for multicellular immunotherapy in neuroblastoma patients

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. (C) 2002 by The American Society of Hematology.