Linked Life Data

20176801

Source:http://linkedlifedata.com/resource/pubmed/id/20176801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-16
pubmed:abstractText
Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4(+) T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3(+) ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4(+) T lymphocytes through the activation of the interleukin-6-STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3-expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4(+) T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1540-9538
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
207
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
505-20
pubmed:dateRevised
2010-9-16
pubmed:meshHeading
pubmed-meshheading:20176801-Antigens, CD, pubmed-meshheading:20176801-CD4-Positive T-Lymphocytes, pubmed-meshheading:20176801-CD8-Positive T-Lymphocytes, pubmed-meshheading:20176801-Disease Progression, pubmed-meshheading:20176801-Endothelium, pubmed-meshheading:20176801-Humans, pubmed-meshheading:20176801-Immune Tolerance, pubmed-meshheading:20176801-Immunosuppression, pubmed-meshheading:20176801-Immunotherapy, pubmed-meshheading:20176801-Lymph Nodes, pubmed-meshheading:20176801-Lymphocyte Activation, pubmed-meshheading:20176801-Lymphoma, Large B-Cell, Diffuse, pubmed-meshheading:20176801-Membrane Proteins, pubmed-meshheading:20176801-Neovascularization, Pathologic, pubmed-meshheading:20176801-RNA, Messenger, pubmed-meshheading:20176801-T-Lymphocytes, pubmed-meshheading:20176801-Transcription, Genetic, pubmed-meshheading:20176801-Vascular Endothelial Growth Factor A
pubmed:year
2010
pubmed:articleTitle
Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion.
pubmed:affiliation
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't