Linked Life Data

21300977

Source:http://linkedlifedata.com/resource/pubmed/id/21300977

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2011-4-22
pubmed:abstractText
Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells. In the present study, we report that EBV-transformed lymphoblastoid B-cell lines (LCLs) and primary PTLDs overexpress galectin-1 (Gal1), a carbohydrate-binding lectin that induces tolerogenic dendritic cells and triggers the selective apoptosis of CD4(+) Th1 and Th17 cells and cytotoxic T cells. In transcriptional reporter assays, LMP2A and LMP1 each increased Gal1-driven luciferase expression, and the combination of LMP2A and LMP1 was additive. In addition, small interfering RNA (siRNA)-mediated depletion of LMP2A decreased Gal1 protein abundance in EBV-transformed LCLs. Gal1 expression in LCLs was dependent on both activating protein 1 (AP-1) and PI3K. A newly developed neutralizing Gal1 mAb selectively inhibited Gal1-mediated apoptosis of EBV-specific CD8(+) T cells. Given the tolerogenic and immunosuppressive function of Gal1, antibody-mediated Gal1 neutralization may represent a novel immunotherapeutic strategy for PTLD and other Gal1-expressing tumors.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4315-22
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders.
pubmed:affiliation
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't