Linked Life Data

18566447

Source:http://linkedlifedata.com/resource/pubmed/id/18566447

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-20
pubmed:abstractText
Vaccination of patients with dendritic cell (DC)/breast carcinoma fusions stimulated antitumor immune responses in a majority of patients with metastatic disease but only a subset demonstrate evidence of tumor regression. To define the factors that limit vaccine efficacy, we examined the biological characteristics of DC/breast carcinoma fusions as APCs and the nature of the vaccine-mediated T cell response. We demonstrate that fusion of DCs with breast carcinoma cells up-regulates expression of costimulatory and maturation markers and results in high levels of expression of IL-12 consistent with their role as activated APCs. Fusion cells also express the chemokine receptor CCR7, consistent with their ability to migrate to the draining lymph node. However, DC/breast cancer fusions stimulate a mixed T cell response characterized by the expansion of both activated and regulatory T cell populations, the latter of which is characterized by expression of CTLA-4, FOXP3, IL-10, and the suppression of T cell responses. Our results demonstrate that IL-12, IL-18, and TLR 9 agonist CpG oligodeoxynucleotides reduce the level of fusion-mediated regulatory T cell expansion. Our results also demonstrate that sequential stimulation with DC/breast carcinoma fusions and anti-CD3/CD28 results in the marked expansion of activated tumor-specific T cells. These findings suggest that DC/breast carcinoma fusions are effective APCs, but stimulate inhibitory T cells that limit vaccine efficacy. In contrast, exposure to TLR agonists, stimulatory cytokines, and anti-CD3/CD28 enhances vaccine efficacy by limiting the regulatory T cell response and promoting expansion of activated effector cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
181
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
808-21
pubmed:dateRevised
2011-2-14
pubmed:meshHeading
pubmed-meshheading:18566447-Antibodies, pubmed-meshheading:18566447-Antigens, CD28, pubmed-meshheading:18566447-Antigens, CD3, pubmed-meshheading:18566447-Breast Neoplasms, pubmed-meshheading:18566447-Cell Differentiation, pubmed-meshheading:18566447-Cell Fusion, pubmed-meshheading:18566447-Cell Proliferation, pubmed-meshheading:18566447-Cells, Cultured, pubmed-meshheading:18566447-Dendritic Cells, pubmed-meshheading:18566447-Humans, pubmed-meshheading:18566447-Interleukin-10, pubmed-meshheading:18566447-Interleukin-12, pubmed-meshheading:18566447-Lymphocyte Activation, pubmed-meshheading:18566447-Mucin-1, pubmed-meshheading:18566447-Oligonucleotides, pubmed-meshheading:18566447-Phenotype, pubmed-meshheading:18566447-Protein Binding, pubmed-meshheading:18566447-Receptors, CCR7, pubmed-meshheading:18566447-T-Lymphocytes, Regulatory
pubmed:year
2008
pubmed:articleTitle
Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-CD3/CD28 promotes the expansion of activated tumor reactive cells.
pubmed:affiliation
Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Brigham & Women's Hospital, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural