Linked Life Data

21389871

Source:http://linkedlifedata.com/resource/pubmed/id/21389871

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-11
pubmed:abstractText
Natural killer (NK) cells have been shown to mediate important immunoregulatory "helper" functions in addition to their cytolytic activity. In particular, NK cells are capable of preventing maturation-related dendritic cell (DC) "exhaustion," inducing the development of "type-1 polarized" mature DCs (DC1) with an enhanced ability to produce interleukin (IL)-12p70, a factor essential for type-1 immunity and effective anticancer responses. Here we show that the NK cell-mediated type-1 polarization of DCs can be applied in the context of patients with advanced cancer to enhance the efficacy of DCs in inducing tumor-specific cytotoxic T lymphocytes. NK cells isolated from patients with late-stage (stage III and IV) melanoma responded with high interferon-? production and the induction of type-1-polarized DCs on exposure to defined combinations of stimulatory agents, including interferon-? and IL-18. The resulting DCs showed strongly-enhanced IL-12p70 production on subsequent T-cell interaction compared with immature DCs (average of 19-fold enhancement) and nonpolarized IL-1?/TNF-?/IL-6/PGE(2)-matured "standard" DCs (average of 215-fold enhancement). Additional inclusion of polyinosinic: polycytidylic acid during NK-DC cocultures optimized the expression of CD80, CD86, CD40, and HLA-DR on the resulting (NK)DC1, increased their CCR7-mediated migratory responsiveness to the lymph node-associated chemokine CCL21, and further enhanced their IL-12-producing capacity. When compared in vitro with immature DCs and nonpolarized standard DCs, (NK)DC1 were superior in inducing functional melanoma-specific cytotoxic T lymphocytes capable of recognizing multiple melanoma-associated antigens and killing melanoma cells. These results indicate that the helper function of NK cells can be used in clinical settings to improve the effectiveness of DC-based cancer vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1537-4513
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
270-8
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:21389871-Antigens, CD, pubmed-meshheading:21389871-Cancer Vaccines, pubmed-meshheading:21389871-Cell Differentiation, pubmed-meshheading:21389871-Cell Movement, pubmed-meshheading:21389871-Cell Polarity, pubmed-meshheading:21389871-Chemokine CCL21, pubmed-meshheading:21389871-Coculture Techniques, pubmed-meshheading:21389871-Cytotoxicity, Immunologic, pubmed-meshheading:21389871-Dendritic Cells, pubmed-meshheading:21389871-Humans, pubmed-meshheading:21389871-Interferon-alpha, pubmed-meshheading:21389871-Interferon-gamma, pubmed-meshheading:21389871-Interleukin-12, pubmed-meshheading:21389871-Interleukin-18, pubmed-meshheading:21389871-Killer Cells, Natural, pubmed-meshheading:21389871-Lymphocyte Activation, pubmed-meshheading:21389871-Melanoma, pubmed-meshheading:21389871-Poly I-C, pubmed-meshheading:21389871-Severity of Illness Index, pubmed-meshheading:21389871-Signal Transduction, pubmed-meshheading:21389871-T-Lymphocytes, Cytotoxic
pubmed:year
2011
pubmed:articleTitle
Helper activity of natural killer cells during the dendritic cell-mediated induction of melanoma-specific cytotoxic T cells.
pubmed:affiliation
Department of Surgery, University of Pittsburgh, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural