Linked Life Data

11882356

Source:http://linkedlifedata.com/resource/pubmed/id/11882356

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-3-7
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-204
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11882356-Animals, pubmed-meshheading:11882356-Antibodies, Monoclonal, pubmed-meshheading:11882356-Antigens, CD4, pubmed-meshheading:11882356-Cell Separation, pubmed-meshheading:11882356-Cells, Cultured, pubmed-meshheading:11882356-Colonic Neoplasms, pubmed-meshheading:11882356-Dendritic Cells, pubmed-meshheading:11882356-Fluorescein-5-isothiocyanate, pubmed-meshheading:11882356-Fluorescent Dyes, pubmed-meshheading:11882356-G(M1) Ganglioside, pubmed-meshheading:11882356-Genetic Engineering, pubmed-meshheading:11882356-Glycosphingolipids, pubmed-meshheading:11882356-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:11882356-Humans, pubmed-meshheading:11882356-Immunotherapy, pubmed-meshheading:11882356-Interleukin-12, pubmed-meshheading:11882356-Interleukin-4, pubmed-meshheading:11882356-Killer Cells, Natural, pubmed-meshheading:11882356-Magnetics, pubmed-meshheading:11882356-Mice, pubmed-meshheading:11882356-Mice, Inbred BALB C, pubmed-meshheading:11882356-Mice, Inbred C57BL, pubmed-meshheading:11882356-Neoplasm Transplantation, pubmed-meshheading:11882356-Neoplasms, Experimental, pubmed-meshheading:11882356-Transfection
pubmed:year
2002
pubmed:articleTitle
Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12.
pubmed:affiliation
Gene Therapy Unit, Department of Internal Medicine, University of Navarra, Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't