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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12
Authors: Rodriguez-Calvillo, M. (Mercedes)
Duarte, M. (Marina)
Tirapu, I. (Íñigo)
Berraondo, P. (Pedro)
Mazzolini, G. (Guillermo)
Qian, C. (Cheng)
Prieto, J. (Jesús)
Melero, I. (Ignacio)
Keywords: Dendritic Cells/immunology
Dendritic Cells/transplantation
Genetic Engineering
Immunotherapy
Interleukin-12/genetics
Killer Cells, Natural/immunology
Neoplasms, Experimental/therapy
Issue Date: 2002
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0301472X01007925
ISSN: 1873-2399
Citation: Rodriguez-Calvillo M, Duarte M, Tirapu I, Berraondo P, Mazzolini G, Qian C, et al. Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12. Exp Hematol 2002 Mar;30(3):195-204.
Abstract
OBJECTIVE: Injection of dendritic cells (DC) engineered with recombinant adenoviral vectors to produce interleukin-12 (IL-12) inside experimental murine tumors frequently achieves complete regressions. In such a system the function of CD8(+) T cells has been shown to be an absolute requirement, in contrast to observations made upon depletion of CD4(+) T cells, which minimally affected the outcome. The aim of this work was to study the possible involvement of natural killer (NK) cells in this setting. MATERIALS, METHODS, AND RESULTS: Depletions with anti-AsialoGM1 antiserum showed only a small decrease in the proportion of complete regressions obtained that correlated with induction of NK activities in lymphatic tissues into which DC migrate, whereas combined depletions of CD4(+) and NK cells completely eliminated the antitumor effects. Likewise in vivo neutralization of interferon-gamma (IFN-gamma) also eliminated those therapeutic effects. Trying to define the cellular role played by NK cells in vivo, it was observed that injection of cultured DC inside the spleen of T- and B-cell-deficient (Rag1(-/-)) mice induced upregulation of NK activity only if DC had been adenovirally engineered to produce IL-12. In addition, identically transfected fibroblasts also activated NK cells, indicating that IL-12 transfection was the unique requirement. Equivalent human DC only activated in vitro the cytolytic and cytokine-secreting functions of autologous NK cells if transfected to express human IL-12. CONCLUSIONS: Overall, these results point out an important role played by NK cell activation in the potent immunotherapeutic effects elicited by intratumoral injection of IL-12--secreting DC and that NK activation under these conditions is mainly, if not only, dependent on IL-12.
Permanent link: http://hdl.handle.net/10171/21789
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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