Linked Life Data

20386464

Source:http://linkedlifedata.com/resource/pubmed/id/20386464

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-4-28
pubmed:abstractText
Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumor immunotherapy. In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2 in patients with metastatic renal cell carcinoma on the frequency of CD4+CD25highFoxp3+ Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P<0.0001). The frequency of Treg cells decreased when patients had been off IL-2 treatment for only 8 days, but remained higher than pretreatment levels. A functional assay showed that isolated Treg cells were capable of inhibiting proliferation of responder cells. Also, in vitro studies showed that coculture of mature DCs, autologous T cells and IL-2 leads to an increase in the number of Treg cells whereas IL-21 does not stimulate the induction of Treg cells. These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4+CD25+Foxp3+ Treg cells in vivo in metastatic renal cell carcinoma patients. Further, the results indicate that the IL-2-induced effect on Treg cells is reversible and declines shortly after termination of IL-2 treatment. Our data suggest that approaches combining DC-mediated immunotherapy and depletion of Treg cells may be necessary to enhance the ability of vaccination therapy to elicit effective antitumor responses in cancer patients. Also, adjuvant IL-21 administration may lead to immune enhancement without simultaneous induction of Treg cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1537-4513
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
425-34
pubmed:meshHeading
pubmed-meshheading:20386464-Adult, pubmed-meshheading:20386464-Aged, pubmed-meshheading:20386464-Antigens, CD4, pubmed-meshheading:20386464-Cancer Vaccines, pubmed-meshheading:20386464-Carcinoma, Renal Cell, pubmed-meshheading:20386464-Cell Proliferation, pubmed-meshheading:20386464-Cells, Cultured, pubmed-meshheading:20386464-Coculture Techniques, pubmed-meshheading:20386464-Dendritic Cells, pubmed-meshheading:20386464-Disease Progression, pubmed-meshheading:20386464-Female, pubmed-meshheading:20386464-Forkhead Transcription Factors, pubmed-meshheading:20386464-Humans, pubmed-meshheading:20386464-Interleukin-2, pubmed-meshheading:20386464-Interleukin-2 Receptor alpha Subunit, pubmed-meshheading:20386464-Interleukins, pubmed-meshheading:20386464-Male, pubmed-meshheading:20386464-Middle Aged, pubmed-meshheading:20386464-Neoplasm Metastasis, pubmed-meshheading:20386464-T-Lymphocytes, Regulatory
pubmed:year
2010
pubmed:articleTitle
Increase of circulating CD4+CD25highFoxp3+ regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2.
pubmed:affiliation
Department of Oncology, Copenhagen University Hospital at Herlev, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase II, Clinical Trial, Phase I