Linked Life Data

20349059

Source:http://linkedlifedata.com/resource/pubmed/id/20349059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-5-27
pubmed:abstractText
Adoptive cell transfer (ACT), either using rapidly expanded tumor infiltrating lymphocytes or T-cell receptor transduced peripheral blood lymphocytes, can be considered one of the most promising approaches in cancer immunotherapy. ACT results in the repopulation of the host with high frequencies of tumor-specific T cells; however, optimal function of these cells within the tumor micro-environment is required to reach long-term tumor clearance. We and others have shown that ongoing anti-tumor immune responses can be impaired by the expression of ligands, such as PD-L1 (B7-H1) on tumor cells. Such inhibitory molecules can affect T cells at the effector phase via their receptor PD-1. PD-L1/PD-1 interaction has indeed been shown crucial in inducing T-cell anergy and maintaining peripheral tolerance. In order to maximize anti-tumor responses, antibodies that target the PD-1/PD-L1 axis are currently in phase I/II trials. Alternatively, a more refined approach could be the selective targeting of PD-1 in tumor-specific T cells to obtain long-term resistance against PD-1-mediated inhibition. We addressed whether this goal could be achieved by means of retroviral siRNA delivery. Effective siRNA sequences resulting in the reduction of surface PD-1 expression led to improved murine as well as human T-cell immune functions in response to PD-L1 expressing melanoma cells. These data suggest that blockade of PD-1-mediated T-cell inhibition through siRNA forms a promising approach to achieve long-lasting enhancement of tumor-specific T-cell function in adoptive T-cell therapy protocols.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1432-0851
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1173-83
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20349059-Animals, pubmed-meshheading:20349059-Antigens, CD274, pubmed-meshheading:20349059-Antigens, CD80, pubmed-meshheading:20349059-Antigens, Differentiation, pubmed-meshheading:20349059-Antigens, Neoplasm, pubmed-meshheading:20349059-Cell Line, Tumor, pubmed-meshheading:20349059-Genetic Vectors, pubmed-meshheading:20349059-Humans, pubmed-meshheading:20349059-Immunotherapy, Adoptive, pubmed-meshheading:20349059-Melanoma, pubmed-meshheading:20349059-Melanoma, Experimental, pubmed-meshheading:20349059-Membrane Glycoproteins, pubmed-meshheading:20349059-Mice, pubmed-meshheading:20349059-Mice, Inbred C57BL, pubmed-meshheading:20349059-Mice, Knockout, pubmed-meshheading:20349059-Mice, Transgenic, pubmed-meshheading:20349059-Peptides, pubmed-meshheading:20349059-RNA, Small Interfering, pubmed-meshheading:20349059-RNA Interference, pubmed-meshheading:20349059-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:20349059-Retroviridae, pubmed-meshheading:20349059-T-Lymphocytes
pubmed:year
2010
pubmed:articleTitle
RNA interference targeting programmed death receptor-1 improves immune functions of tumor-specific T cells.
pubmed:affiliation
Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, 1066 CX, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't